Ingestive Behavior, Survival, and Reproductive Success

Hormones and Behavior 64 (2013) 702–728

Contents lists available at ScienceDirect

Hormones and Behavior

journal homepage: www.elsevier.com/locate/yhbeh

Review When do we eat? Ingestive behavior, survival, and reproductive success

Jill E. Schneider a,⁎, Justina D. Wise a,NoahA.Bentona,JeremyM.Brozeka, Erin Keen-Rhinehart b a Department of Biological Sciences, Lehigh University, 111 Research Drive, Bethlehem, PA 18015, USA b Department of Biology, Susquehanna University, Selinsgrove, PA 17870, USA View metadata, citation and similar papers at core.ac.uk brought to you by CORE

provided by Elsevier - Publisher Connector article info abstract

Article history: The neuroendocrinology of ingestive behavior is a topic central to human health, particularly in light of the Received 18 February 2013 prevalence of obesity, eating disorders, and diabetes. The study of food intake in laboratory rats and mice Revised 21 July 2013 has yielded some useful hypotheses, but there are still many gaps in our knowledge. Ingestive behavior is Accepted 22 July 2013 more complex than the consummatory act of eating, and decisions about when and how much to eat usually Available online 30 July 2013 take place in the context of potential mating partners, competitors, predators, and environmental fluctuations that are not present in the laboratory. We emphasize appetitive behaviors, actions that bring animals Keywords: Appetitive behavior in contact with a goal object, precede consummatory behaviors, and provide a window into motivation. Consummatory behavior Appetitive ingestive behaviors are under the control of neural circuits and neuropeptide systems that con- Food intake trol appetitive sex behaviors and differ from those that control consummatory ingestive behaviors. Food hoarding Decreases in the availability of oxidizable metabolic fuels enhance the stimulatory effects of peripheral Hunting hormones on appetitive ingestive behavior and the inhibitory effects on appetitive sex behavior, putting Prey catching a new twist on the notion of leptin, insulin, and ghrelin “resistance.” The ratio of hormone concentrations Metabolic fuels to the availability of oxidizable metabolic fuels may generate a critical signal that schedules conflicting be- Reproductive behavior haviors, e.g., mate searching vs. foraging, food hoardingvs.courtship,andfataccumulationvs.parental Sex behavior “ ” Vaginal scent marking care. In species representing every vertebrate taxaandeveninsomeinvertebrates,manyputative satiety or “hunger” hormones function to schedule ingestive behavior in order to optimize reproductive success in environments where energy availability fluctuates. © 2013 The Authors. Published by Elsevier Inc. Open access under CC BY-NC-ND license.

Contents

Introduction...... 703 Neuroendocrinologyoffoodintakeinlaboratoryratsandmice...... 703 Adistributedneuralnetworkcontrolsfoodintake...... 704 Thearcuateperspective...... 707 Evidencethatdeemphasizesthearcuateincontroloffoodintake...... 708 Appetitiveingestivebehavior...... 709 Historicalperspectiveonappetitivebehaviorandmotivation...... 709 Foodhoarding...... 710 Huntingandpreycatching...... 711 Summaryofappetitivebehaviors...... 711 Reasonstostopeating...... 712 Thechoicebetweeneatingandmating...... 712 PreferenceforfoodormalesinSyrianhamsters...... 712 Thechoicebetweenfoodandsexinotherspecies...... 715 Courtshipandeatinginsemelparousspecies...... 717 EnergyavailabilityandtheHPGsystem...... 717 Summaryandconclusions...... 719

⁎ Corresponding authors at: Department of Biological Sciences, 111 Research Drive, Bethlehem, PA 18015, USA. Fax: +1 610 758 4004.

0018-506X © 2013 The Authors. Published by Elsevier Inc. Open access under CC BY-NC-ND license. http://dx.doi.org/10.1016/j.yhbeh.2013.07.005 J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 703

Acknowledgments...... 719 References...... 720

Introduction behaviors and orexigenic, anabolic hormones inhibit reproductive behaviors. The idea that so-called hunger and satiety hormones function A clinical perspective on human obesity suggests that we are eating to maintain a particular level of body weight or adiposity is incomplete ourselves “to death” (Shelton and Miller, 2010). According to this per- without the understanding that reproductive success depends upon fluc- spective, some combination of genes, diet, and lifestyle promotes over- tuations in adiposity and the ability to gain access to stored energy in ad- eating and/or low energy expenditure, which leads to a putative disease iposetissue(Schneider and Watts, 2002, 2009; Wade and Schneider, known as obesity and its myriad adverse health consequences (Vetter 1992). et al., 2010). A biological perspective, however, suggests that many phe- We begin with a brief overview of chemical messengers that influ- notypes we see today have been molded by natural selection; they were ence food intake in laboratory rats and mice studied in isolation from maintained in populations over generations because they were adap- opposite-sex conspecifics and without behavioral options. Next, we tive, i.e., they increased reproductive success. If natural selection was a consider the perspective developed from experiments using other primary architect of the mechanisms that control ingestive behavior, mammalian species and a few from other vertebrate taxa. We empha- we might gain key insights by studying their link to reproductive suc- size a small number of experiments in which energetic variables are cess. In other words, we need to know how we eat ourselves to life. manipulated, thereby calling attention to the need for more such exper- We need to determine how putative orexigenic and anorectic hormones iments. Specifically, it would be instructive to examine ingestive and re- schedule ingestive behavior in order to optimize reproductive success. productive processes under conditions in which the following variables Most often, controls of food intake are assumed to function primarily are manipulated: food availability, ambient temperature, the amount of to maintain homeostasis. As noted by Friedman (2008), homeostasis is energy expended on exercise, and the presence or absence of competi- from the Latin words for staying “similar to,” not “the same as,” and tors and potential mating partners. thus it implies both fluctuation and maintenance. The variable that In addition, we emphasize the need to consider appetitive as well as must be maintained in equilibrium is metabolic fuel availability, not consummatory behaviors. These behaviors provide a window into mo- body weight, adiposity, or food intake. Food intake, body fat storage, tivation, and, in many cases, motivation is under the control of neural and energy expenditure often fluctuate wildly in order to maintain circuits and neuropeptide systems that differ from those that control energy homeostasis, i.e., homeostasis in the availability and flux of oxi- performance. So-called anorectic peptides enhance sexual motivation dizable metabolic fuels (Friedman, 2008). whereas orexigenic peptides inhibit sexual motivation, often with no Energy for cellular processes and organismal activity comes from effect on sexual performance. Chemical messengers control moment- eating food. In typical laboratory environments, animal subjects have to-moment decisions about whether to engage in courtship, parental ad libitum access to readily available food. In most natural habitats, behavior, ingestive behavior, migration, territoriality, and/or aggression. however, food supplies fluctuate, and animals must expend energy to Furthermore, the effects of these chemical messengers on behavior dif- find and procure food (Bronson, 1989). In the wild, both survival and fer according to subtle changes in food availability, body fat content, and reproduction require anticipatory overeating, food storage, and meta- the availability of oxidizable metabolic fuels. When energetic demands bolic adaptations to fasting. It is not surprising then that most vertebrate are low, there is ample food available to eat, and animals can access species show metabolic transformations that allow the breakdown of metabolic fuels from their adipose tissue stores, there is a pool of oxidiz- bodily tissue in order to fuel activity during fasting and starvation able metabolic fuels that can support cellular process, activity, immune (Wang et al., 2006). Reproductive processes, including gametogenesis, function and reproduction. This is depicted by the full tank in Fig. 1A. vitellogenesis, fetal and embryonic development, lactation (in mam- Frank starvation (e.g., total food deprivation in lean animals or in fat- mals), and parental care are energetically expensive, and these process- tened animals deprived for prolonged periods) inhibits the hypotha- es can be delayed to conserve energy for survival under harsh energetic lamic–pituitary–gonadal (HPG) system, leaving enough metabolic conditions (Cooke et al., 2006; Gittleman and Thompson, 1988; Sibly fuels for survival (depicted by the drained liquid in Fig. 1Bandreviewed et al., 2012; Van Dyke and Beaupre, 2011). Behavioral phenotypes that by I'Anson et al., 1991; Schneider, 2004; Wade and Jones, 2004; Wade were molded by natural selection, including the controls of ingestive and Schneider, 1992). In contrast to severe energetic challenges, mild behavior, likely increased reproductive success or helped individuals energetic challenges (e.g., less than 25% food restriction in fattened an- survive to realize their reproductive potential (Darwin, 1859). imals) interact with hormone and neuropeptide action to produce fluc- Behaviors, including sex and ingestive behaviors, are critical in ener- tuations in the motivation to engage in sex and ingestive behavior, gy homeostasis. Experiments designed to measure the metabolic costs depicted in Fig. 1C. Effects of mild restriction can change sensitivity to of reproductive processes revealed that the most important adaptation sex hormones without impact on steroid secretion (Klingerman et al., to fluctuating energy availability is behavioral compensation (reviewed 2010, 2011a, 2011b; Schneider, 2006; Schneider et al., 2007, 2012). by Gittleman and Thompson, 1988). Examples include those species If most of these chemical messengers evolved to orchestrate conflicting that overeat and store energy on the body as adipose tissue prior to mat- appetites on a moment-to-moment basis, it is not surprising that any ing so as to meet the future energetic demands of gestation; species in one of these alone fails to prevent or reverse obesity. Understanding which pregnant females conserve energy for their growing conceptus neuroendocrine control of behavior in a dynamic energetic environ- by reducing flight, locomotion and/or general activity; species of ment will be crucial as we face the problems of global climate change, birds that relax their homeothermy during incubation; and species in endocrine disruptors in the environment, and rising obesity in human which lactating female mammals increase food intake or draw upon a beings, pets, and wildlife (Humphries et al., 2004; Wingfield, 2008). food cache or their own adipose tissue (reviewed by Gittleman and Thompson, 1988). Thus, behavioral flexibility allows adaptation to a la- Neuroendocrinology of food intake in laboratory rats and mice bile energetic environment, and this idea is central to the behavioral neuroendocrinology of ingestive behavior. We suggest that a primary In the vast majority of experiments on ingestive behavior, the model role of hormones is to orchestrate these changes in behavioral priorities. system is either laboratory rats or mice (Rattus norvegicus and Mus Anorectic, catabolic hormones often stimulate or permit reproductive musculus), and the behavioral end point is food intake, the amount of 704 J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728

peripheral hormones, leptin from the adipocyte, ghrelin from the stomach, cholecystokinin (CCK) and glucagon-like peptide-I (GLP-I) from the gut, and their targets in the hypothalamus have garnered a great deal of interest. More recently, attention has turned back toward the HPG, HPA, and HPI axes (hypothalamic–pituitary–adrenal in mammals, birds, and reptiles, and the hypothalamic–pituitary–interrenal in fish and amphibians). These so-called sex and stress hormones have major influences on ingestive behavior. Estradiol, secreted primarily from the ovary but also the adrenals, decreases food intake and body weight (Gray and Wade, 1981; Wade and Gray, 1979; Wade et al., 1985), and genetic knock out of estrogen receptor results in obesity (Geary et al., 2001; Heinen et al., 2000; Musatov et al., 2007; Ohlsson et al., 2000). Gonadotropin-releasing hormone-II (GnRH-II) and gonadotropin- inhibiting hormone (GnIH) influence both sex and ingestive behavior (Clarke et al., 2012; Hoskins et al., 2008; Kauffman et al., 2005, 2006; Klingerman et al., 2011b; Tachibana et al., 2005). The obesity caused by lesions, diet, neuropeptide Y (NPY) treatment, or mutations in the gene for leptin can be reversed by adrenalectomy or simultaneous knock out of genes that inhibit glucocorticoid secretion (Wang et al., 2012 and reviewed by Heinrichs and Richard, 1999). Furthermore, glucocorticoids and gonadal steroids alter the development of the neural circuits that govern metabolism, adipose tissue distribution, and ingestive behavior (Gao et al., 2007). The importance of adrenal and gonadal steroids is magnified because these hormones play a major role in coor- dinating ingestive behavior with the environment. Future research should focus on the interactions among hormones, environmental energy, and cues from potential mating partners. Food intake in laboratory rodents is most often measured as the size and frequency of meals. In animals housed in isolation with unlimited food, food intake is affected by at least three important interacting factors 1) sensory signals generated by the interaction of food with the gastrointestinal tract, 2) metabolic consequences of digestion, absorption, and the breakdown of macronutrients (fats, carbohydrates, and proteins) into oxidizable metabolic substrates (mainly glucose and free fatty acids), and 3) hormonal signals that vary with 1 and 2, and some that vary with lipogenesis and adipose tissue cell size.

A distributed neural network controls food intake

Signals from the periphery influence food intake via the ascending visceral afferent pathway (Fig. 2), which projects from many peripheral sensory organs via the vagus nerve to a distributed neural Fig. 1. The pool of oxidizable metabolic fuels is depicted as the liquid panels A, B, and C. network throughout the brain (reviewed by Grill, 2006, 2010). The pro- These fuels can be chemically transformed to be stored as glycogen in muscle or lipids cess of meal termination begins with sensations generated by gut dis- in adipose tissue (the tank on the left), and used for maintenance of the reproductive system, all behaviors, and cellular processes (the tree on the right). When energy demands tension and also by increases in the supply of oxidizable fuels. Some of are low and energy intake and storage are high, sufficient levels of oxidizable fuels are these sensations are carried to the brain by the vagus nerve. These sen- available for both survival and reproduction (A). When food is not available, animals hy- sations generate neural and hormonal signals in the gut, liver, or other drolyze and mobilize fuels from their fat stores, and when the availability of fuels is low, peripheral organs. Examples of metabolic sensory stimuli include the the hunger for food is urgent, and the reproductive and immune system can be inhibited decrease in hepatic energy status brought about by treatments that to conserve fuels necessary for survival (symbolized by the roots) (B). Mild energetic challenges can inhibit sexual motivation and appetitive sex behavior (symbolized by the block fuel oxidation, deplete adenosine triphosphate (ATP), or decrease leaves), increase hunger, and the response to anorectic or orexigenic hormones without its phosphorylation potential. These metabolic manipulations increase inhibition of the hypothalamic–pituitary–gonadal (HPG) system (symbolized by the tree food intake, and the increases are blocked by surgical transection of trunk) (C). the vagus nerve, a procedure that cuts the neural connections between many peripheral organs (but not from brown or white adipose tissue) and the brain (Friedman et al., 2003; Horn et al., 2004; Ji et al., 2000; la Fleur et al., 2003; Rawson et al., 2003). In addition, the interaction food consumed per unit time by animals housed in isolation. Early endo- of food with the gut stimulates the secretion of gastrointestinal hor- crinologists discovered that food intake is influenced by stressors, adre- mones, including CCK, GLP-I, and peptide YY3-36. Post-ingestive in- nalectomy, and treatment with adrenal steroids (Stevenson and creases in hormones stimulate receptors on vagal afferent neurons in Franklin, 1970). In addition, food intake is influenced by the ovulatory the vagal nodose ganglion. The activated cells in the nodose ganglion cycle, gonadectomy, and treatment with gonadal steroids (Wade and send afferent signals to the nucleus tractus solitarius, a.k.a., the nucleus Zucker, 1970). Since that time, the list has grown to over 40 different of the solitary tract (NTS), which has reciprocal connections to the chemical messengers that either increase or decrease food intake area postrema (AP) (e.g., Huo et al., 2007; Powley, 2000). NTS cells when administered to rats or mice (Table 1, reviewed by Schneider send information about peripheral fuel availability and gut distension et al., 2012; Schneider and Watts, 2002). In the last decade, the to many regions in the brain, including the lateral parabrachial nucleus J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 705

Table 1 A partial list of chemical messengers with effects on ingestive behavior and reproductive behavior in representative species from the vertebrate taxa.

Central “Orexigenic” Agents Ingestive Effects Reproductive Effects

Agouti-related protein (AgRP), HS04, SHU9119 Increases food intake in ﬁsh (Schjolden et al., 2009), birds Inhibits gonadotropin secretion in ﬁsh (Zhang et al., 2012), (MCR antagonists) (Strader et al., 2003), and mammals (Rossi et al., 1998; Stark, inhibits LH in the presence of estradiol in female rats (Schioth 1998), and food hoarding in hamsters (Day and Bartness, 2004) et al., 2001; Watanobe et al., 1999), stimulates LH in male mammals (Stanley et al., 1999), ablation of AgRP gene restores fertility in ob/ob mice (Wu et al., 2012)

Alarin Increases food intake in male rats (Van Der Kolk et al., 2010) Stimulates LH secretion in castrated male rats (Van Der Kolk et al., 2010)

β-Endorphin Increases food intake in fish (de Pedro et al., 1995b)(reviewed Mediates stress-induced suppression of LH in fish (Ganesh in Lin et al., 2000), birds (Deviche and Schepers, 1984; Maney and Chabbi, 2013), birds (Sakurai et al., 1986), inhibits LH and Wingfield, 1998; Yanagita et al., 2008), and rats (Grandison secretion and sexual performance (Hughes et al., 1987, 1990; and Guidotti, 1977; McKay et al., 1981) Sirinathsinghji et al., 1983), but might also increase sexual motivation in rats (Mitchell and Stewart, 1990; Torii et al., 1999)

Galanin Increases food intake in ﬁsh (De Pedro et al., 1995a; Lin et al., Stimulates LH secretion in birds (Hall and Cheung, 1991), 2000; Nelson and Sheridan, 2006; Volkoff et al., 2005)and steroid-primed rats (Sahu et al., 1987) rats (Kyrkouli et al., 1990)

Galanin-like peptide (GALP) Increases food intake in rats (Matsumoto et al., 2002), also Stimulates LH secretion in male mice and rats and in decreases food intake in mice (Krasnow et al., 2003) estradiol-treated female rats (Krasnow et al., 2003; Matsumoto et al., 2001; Uenoyama et al., 2008)

Gamma aminobutyric acid (GABA) Might not mediate hyperphagic effects of orexin in ﬁsh Increases gonadotropin release in ﬁsh (Kah et al., 1992); (Facciolo et al., 2011); increases food intake in rats (Basso GABA-BR decreases excitability of mouse GnRH-I neurons and Kelley, 1999) (Zhang et al., 2009); GABA-AR excitatory for mouse GnRH-I neurons (DeFazio et al., 2002; Moenter and DeFazio, 2005)

Melanin-concentrating hormone (MCH) Increases food intake in rats (Presse et al., 1996), but decreases Inhibits LH secretion in rats (Tsukamura et al., 2000a) food intake in ﬁsh (Shimakura et al., 2008)

Neuropeptide Y (NPY) Increases food intake in ﬁsh (de Pedro et al., 2000; Increases gonadotropin release in ﬁsh (Peng et al., 1993), Lopez-Patino et al., 1999), frogs (Crespi et al., 2004), snakes inhibits steroid biosynthesis in frogs (Beaujean et al., 2002), (Morris and Crews, 1990), birds (Strader and Buntin, 2001), inhibits sex behavior in snakes (Morris and Crews, 1990), rats (Stanley and Leibowitz, 1984) and food hoarding in inhibits LH in the absence of estradiol, stimulates LH in the hamsters (Dailey and Bartness, 2009) presence of estradiol in rats (Crowley et al., 1985; Sahu et al., 1987)(Sahu et al., 1987), inhibits sex behavior in rats (Ammar et al., 2000)

Orexin/hypocretin Increases food intake in ﬁsh (Lin et al., 2000; Volkoff et al., Inhibits spawning in ﬁsh (Hoskins et al., 2008), inhibits LH 1999; Volkoff et al., 2005), and rats (Sakurai et al., 1998), in rats with little or no estradiol (Furuta et al., 2002), but not in birds (da Silva et al., 2008) stimulates LH in rats with high levels of estradiol (Pu et al., 1998)

Gonadotropin inhibiting hormone (GnIH) Increases food intake in birds (Tachibana et al., 2005), mice, Inhibits GnRH and LH secretion and sex behavior in ﬁsh sheep, and monkeys (Clarke et al., 2012; Johnson et al., 2007; (Moussavi et al., 2012), birds (Bentley et al., 2006; Satake Tachibana et al., 2005) et al., 2001) and blocks the LH surge in sheep and inhibits LH secretion in rats and female hamsters (Bentley et al., 2006; Johnson et al., 2007; Kriegsfeld et al., 2006; Smith et al., 2008)

Peripheral “Orexigenic” Hormones Ingestive Effects Reproductive Effects

Corticosteroids Chronically elevated levels increase food intake in ﬁsh (Bernier Inhibits a wide array of reproductive parameters in ﬁsh et al., 2004), amphibians (Crespi et al., 2004), birds (Astheimer including parental behavior (Carragher et al., 1989; O'Connor et al., 1992), and rats (Hamelink et al., 1994; McLaughlin et al., et al., 2009)reviewedby(Milla et al., 2009), inhibits steroid 1987; Stevenson and Franklin, 1970) synthesis and spermatogenesis in amphibians (Moore and Zoeller, 1985; Moore and Jessop, 2003), inhibits sex behavior in snakes (Lutterschmidt et al., 2004; Moore and Jessop, 2003), stimulates gonadotropin secretion at low doses in birds (Etches and Cunningham, 1976), inhibits HPG function at chronically high doses in birds (Etches et al., 1984), and mammals (Vreeburg et al., 1988)

Ghrelin (gut) Increases food intake in fish (goldfish and tilapia), but decreases Stimulates LH release from fish (Grey et al., 2010), inhibits food intake in rainbow trout (Jonsson, 2013; Jonsson et al., 2010), GnRH, LH secretion and sex behavior in rats and mice decreases food intake in birds (Kaiya et al., 2009), increases food (Fernandez-Fernandez et al., 2004; Furuta et al., 2001; Shah intake in rats and mice (Tschop et al., 2000; Wren et al., 2000) and Nyby, 2010) and food hoarding in Siberian hamsters (Keen-Rhinehart and Bartness, 2005)

Insulin (pancreas) Chronically elevated levels increase body weight, adiposity, Systemic treatment inhibits LH secretion at doses that and food intake in birds (Nir and Levy, 1973), rats (Booth and increase food intake in hamsters not allowed to overeat Brookover, 1968; Friedman, 1977; Friedman et al., 1982; Houpt, (Wade et al., 1991), inhibits LH secretion in sheep treated 1974) peripherally with saline but not with glucose (Clarke et al., 1990)

Motilin (gut) Increases food intake in fasted rats (Garthwaite, 1985) Inhibits LH secretion in rats (Tsukamura et al., 2000b)

Progesterone (gonads, adrenals) Reverses the weight reducing effects of estradiol on body weight Synergizes with estradiol to stimulate female sexual andfoodintakeinrodents(Hervey and Hervey, 1966, 1969; performance in rats (Dempsey et al., 1936), enhances Zucker et al., 1972) estradiol feedback on LH in female rats (Chappell and Levine, 2000), mimics testosterone in male rats (Witt et al., 1995)

(continued on next page) 706 J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728

Table 1 (continued) PeripheralCentral “Orexigenic“Orexigenic” Agents” Hormones Ingestive Effects Reproductive Effects

Testosterone (gonads, adrenals) Increases food intake and growth in rats (Siegel et al., 1981) Stimulates sexual motivation in females (de Jonge et al., 1986; Everitt and Herbert, 1970) and sexual performance in male rats (Davidson, 1966; Davidson and Bloch, 1969)

Central “Anorectic” Agents Ingestive Effects Reproductive Effects

α-Melanocyte stimulating hormone (a-MSH), Decreases food intake in ﬁsh (Kang et al., 2011; Schjolden Enhances electric organ discharge in electric ﬁsh (Markham melanotan-II (MT-II), PT-141 et al., 2009), amphibians (Carpenter and Carr, 1996), birds et al., 2009), stimulates LH secretion and sex behavior in rats (Kawakami et al., 2000; Tachibana et al., 2007), and rats (Alde and Celis, 1980; Thody et al., 1981) (Vergoni et al., 1986), and food hoarding in Siberian hamsters (Keen-Rhinehart and Bartness, 2007a; Shimizu et al., 1989)

Cocaine and amphetamine-regulated Decreases food intake in ﬁsh (Volkoff et al., 2005), birds Stimulates GnRH secretion in rats (Lebrethon et al., 2000; transcript (CART) (Tachibana et al., 2003), rats (Kristensen et al., 1998) Parent et al., 2000)

Cholecystokinin (CCK) Decreases food intake in ﬁsh (Himick and Peter, 1994; Stimulates GnRH and LH secretion in rats (Ichimaru et al., Volkoff et al., 2005), birds (Tachibana et al., 2012), rats 2003; Kimura et al., 1983) (Gibbs et al., 1973) and food hoarding in Siberian hamsters CCK in the medial preoptic areas is required for estradiol- (Bailey and Dela-Fera, 1995; Figlewicz et al., 1989; Teubner induced lordosis in rats (Dornan et al., 1989; Holland and Bartness, 2010) et al., 1997)

Corticotropin releasing hormone (CRH) Decreases food intake in ﬁsh (De Pedro et al., 1993; Matsuda Inhibits spawning in ﬁsh (Mousa and Mousa, 2006), inhibits et al., 2008), amphibians (Crespi et al., 2004), birds (Denbow LH secretion and lordosis in rats (Olster and Ferin, 1987)and et al., 1999; Furuse et al., 1997), rats (Heinrichs and Richard, sexbehaviorinSyrianhamsters(Jones et al., 2002) 1999; Levine et al., 1983; Morley and Levine, 1982; Negri et al., 1985) and food hoarding in rats (Cabanac and Richard, 1995) reviewed by (Carr, 2002)

Dopamine (DA) Decreases food intake in ﬁsh (Leal et al., 2013), rats (Heffner Inhibits gonadotropin secretion in ﬁsh (Omeljaniuk et al., et al., 1977), increases food hoarding in rats (Borker and 1989), stimulates sexual arousal, motivation and reward Mascarenhas, 1991; Kelley and Stinus, 1985), and reward in birds (Cornil et al., 2005), rats and hamsters (Agmo (Wise, 2004) and Picker, 1990; Meisel and Mullins, 2006)

Glucagon-like peptide (GLP-I) Decreases food intake in ﬁsh (Silverstein et al., 2001), birds Stimulates LH secretion (Beak et al., 1998) (Tachibana et al., 2006), rats (Turton et al., 1996)

Gonadotropin releasing hormone Decreases food intake in ﬁsh (Hoskins et al., 2008; Nishiguchi Stimulates LH secretion in ﬁsh (Moussavi et al., 2012), (GnRH I or II) et al., 2012), and female musk shrews (Kauffman and Rissman, birds (Chowdhury and Yoshimura, 2004), stimulates LH 2004b) secretion and sex behavior in amphibians and reptiles (Alderete et al., 1980; Licht et al., 1984), rats and sheep and sex behavior in shrews and mice (Kauffman and Rissman, 2004a; Kauffman et al., 2005)(Temple et al., 2003)(Moss and McCann, 1975)(Clarke and Cummins, 1982)

Insulin-like Growth Factor-1 (IGF-I in CNS) ICV treatment decreases food intake in diabetic, but not Restores LH surge amplitude in middle-aged rats (Todd normal rats (Lu et al., 2001), required for post-fast hyperphagia et al., 2010), required for the LH surge, estrous behavior, in rats (Todd et al., 2007) estrous cycles in rats (Etgen and Acosta-Martinez, 2003; Quesada and Etgen, 2002; Todd et al., 2007), and for sex behavior in rats (Etgen and Acosta-Martinez, 2003)

Kisspeptin Decreases food intake in mice (Stengel et al., 2011) Stimulates GnRH and LH secretion in ﬁsh (Moussavi et al., 2012; Tena-Sempere et al., 2012), stimulates testicular expression of ER-a in frogs (Chianese et al., 2013), rats (Gottsch et al., 2004; Irwig et al., 2004)

Norepinephrine Decreases food intake in birds (Denbow, 1983)andstimulates InhibitsLHsecretioninrats(Iwata et al., 2011), stimulates food intake in rats (Ritter and Epstein, 1975) sex behavior in birds (Cornil et al., 2005)andrats(Nock and Feder, 1979)

Oxytocin Decreases food intake in birds (Jonaidi et al., 2003), rats Stimulates GnRH and LH secretion sex behavior in rats (Olson et al., 1991) (Rettori et al., 1997; Whitman and Albers, 1995)

Secretin (move to VIP) Decreases food intake in rats (Cheng et al., 2011a) Stimulates LH secretion in rats (Babu and Vijayan, 1983)

Serotonin (5HT) Decreases food intake in birds (Denbow et al., 1982), rats Stimulates LH in the presence of estradiol in rats (Coen (Blundell, 1977) and MacKinnon, 1979) inhibits LH secretion in the absence of estradiol in rats (Coen et al., 1980)(Koh et al., 1984)

Thyrotropin releasing hormone Decreases food intake in rats (Vijayan and McCann, 1977) Stimulates LH secretion in pituitary in vitro not in vivo in and Siberian hamsters (Steward et al., 2003) rats (Fujihara and Shiino, 1983), and indirectly by effects on thyroid hormones in rats (Barrett et al., 2007)

Urocortin Decreases food intake in ﬁsh, amphibians, birds, and rats Stimulates LH secretion in ewes (Holmberg et al., 2001), (Spina et al., 1996) inhibits LH secretion in rats (Li et al., 2005; Nemoto et al., 2010), directly inhibits Leydig cell function in rats (Rivier, 2008)

Peripheral “Anorectic” Hormones Ingestive Effects Reproductive Effects

Adiponectin (adipocytes) Decreases food intake in rats (Bassi et al., 2012), increases Implicated in embryo implantation and fetal development food intake in mice (Kubota et al., 2007), decreases body in pigs and women (Palin et al., 2012), inhibits ovarian weight and increases energy expenditure, insulin sensitivity, steroidogenesis in cows (Lagaly et al., 2008), inhibits GnRH and ffa oxidation without effect on food intake in rats (Fruebis and LH in rats and in GnRH cell cultures (Cheng et al., 2011b; et al., 2001; Qi et al., 2004) Lu et al., 2008) J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 707

Table 1 (continued) CentralPeripheral“Orexigenic“Anorectic” Agents” Hormones Ingestive Effects Reproductive Effects

Adrenocorticotropic hormone (ACTH) Decreases food intake in rats (Vergoni et al., 1986) Stimulated LH secretion in female rats inhibits LH secretion in male rats (indirect via adrenals) (Mann et al., 1985; Putnam et al., 1991)

Bombesin (gut) Decreases food intake in ﬁsh (Volkoff et al., 2005), birds Stimulates LH secretion in rats (Babu and Vijayan, 1983) (Savory and Hodgkiss, 1984; Tachibana et al., 2010), and rats (Gibbs et al., 1979)

Cholecystokinin (gut) Decreases food intake in ﬁsh (Volkoff et al., 2005), birds Stimulates LH secretion in rats (Perera et al., 1993); (Savory and Hodgkiss, 1984), and hoarding in Siberian inhibits lordosis duration in rats (Mendelson and Gorzalka, hamsters (Gibbs et al., 1973; Qian et al., 1999; Teubner and 1984), but see central effects in Table 1.1 Bartness, 2010)

Estradiol (gonads, adrenals, adipocytes, brain) Decreases body weight and food intake in ﬁsh (Leal et al., Stimulates sexual receptivity and vitellogenesis and has negative 2009), lizards (Shanbhag and Prasad, 1992), obese but not feedback on LH in ﬁsh, frogs, lizards and birds (Chakraborty and lean hens (Jaccoby et al., 1995; Jaccoby et al., 1996), rats Burmeister, 2009; Cheng, 1973; Crews, 1975; Gavaud, 1986; (Nunez et al., 1980; Roepke et al., 2010; Roy and Wade, Gibbins and Robinson, 1982a,1982b; Licht et al., 1985; Liley, 1977; Zucker, 1969) and food hoarding in Syrian hamsters 1972; Mason and Adkins, 1976; McCreery and Licht, 1984; (Klingerman et al., 2010) Redshaw et al., 1969; Shanbhag and Prasad, 1992; Yu et al., 1981), and stimulates LH surges in female rats (Chazal et al., 1974) and female sex behavior in rats (Dempsey et al., 1936; Powers, 1970), increases courtship and sexual behaviors in hamsters (Ciaccio and Lisk, 1973; Ciaccio et al., 1979; Takahashi et al., 1985)

Insulin (ICV treatment) Decreases food intake in rats and baboons (Chavez et al., Stimulates LH pulses in rats, pigs, and diabetic sheep and non 1995; Woods et al., 1979) diabetic ovariectomized sheep (Bucholtz et al., 2000; Cox et al., 1987; Daniel et al., 2000; Kovacs et al., 2003; Miller et al., 1995), inhibits LH in ad libitum-fed ovariectomized lambs (Hileman et al., 1993)

Insulin-like growth factor Increases body weight gain at superphysiological concentrations Does not accelerate reproductive development in female rats (Gruaz et al., 1997) (Gruaz et al., 1997)

Leptin (adipocytes, liver) Decreases body weight, adiposity, and food intake in fish Mammalian leptin increases gonadotropin secretion in fish (Crespi and Denver, 2006; Murashita et al., 2008), and (Peyon et al., 2003; Peyon et al., 2001), delays the summertime mice (Campfield et al., 1995; Halaas et al., 1995; regression of the testes in lizards (Putti et al., 2009), delays Pelleymounter et al., 1995) and food hoarding in Syrian fasting-induced cessation of egg laying, follicular regression, and hamsters (Buckley and Schneider, 2003) while increasing follicle wall apoptosis in chickens (Paczoska-Eliasiewicz et al., energy expenditure 2003), reverses the effects of metabolic challenges on gonadotropin secretion in mice (Ahima et al., 1996; Barash et al., 1996), estrous cycles, and steroid-induced sex behavior (the latter only in ad libitum fed female hamsters) (Schneider et al., 2007; Schneider et al., 1997; Wade et al., 1997)

Resistin Transient decreases in food intake in rats (Tovar et al., 2005) Promotes ovarian steroid secretion in rats (Maillard et al., 2011)

(PBN), the hypothalamus, and the basal forebrain (Fig. 2)(Huo et al., AgRP is an antagonist. A relatively simple hypothesis holds that NPY/ 2007; Powley, 2000). AgRP and POMC/CART peptides are responsive to gastric signals mediated by peripheral hormones. There are receptors for peripheral hor- The arcuate perspective mones such as leptin, insulin, and ghrelin on Arc cells, including NPY/ AgRP and POMC/CART cells. Effects of these peripheral hormones on In addition, other peripheral signals such as insulin, leptin, and NPY/AgRP and POMC/CART gene transcription are consistent with ghrelin can influence food intake by action on receptors in the hypothal- their effects on food intake (Coppari et al., 2005; Perello et al., 2012; amus as well as other brain areas. In terms of the number of articles pub- Williams et al., 2010). For example, leptin treatment decreases meal lished, most work in laboratory rodents has emphasized the arcuate size, binds to leptin receptor (LepR) on both NPY/AgRP and POMC/ nucleus of the hypothalamus (Arc) as a primary controller of ingestive CART cells, increases cellular activation and gene transcription of behavior in response to insulin, leptin, and ghrelin (depicted in Fig. 3; POMC precursor peptide, and the effects of leptin are blocked by treat- reviewed by Barsh and Schwartz, 2002; Crowley et al., 2001; Schwartz ment with antagonists to the MC4 receptor. Peripheral hormones affect and Porte, 2005; Zigman and Elmquist, 2003). Keeping in mind that not only the release of neuropeptides but also the synaptic input into the number of papers published on a nucleus is a poor judge of its im- NPY/AgRP and POMC/CART cells (reviewed by Briggs and Andrews, portance, within the Arc, two well-studied orexigenic peptides are 2011; Eckel, 2011; Gao et al., 2007; Gyengesi et al., 2010; Zigman and found, often within the same cell body: NPY and agouti-related protein Elmquist, 2003). (AgRP). Orexigenic effects of NPY and AgRP are thought to be Recent evidence suggests that AgRP cells are uniquely positioned so counterbalanced by the anorectic peptides of the Arc: cocaine and as to receive signals from peripheral hormones that reflect energy flux. amphetamine-regulated transcript (CART) and α-melanocyte stimulat- During the development of obesity and high-fat diet-induced leptin ing hormone (α-MSH), the latter being a cleavage product of the resistance, AgRP cells might act as sentinels that monitor decreases in proopiomelanocortin (POMC) gene (reviewed by Schwartz and Porte, plasma leptin concentrations. AgRP neurons are the predominant cell 2005; Zigman and Elmquist, 2003). Both α-MSH and AgRP act via type situated outside the blood–brain barrier, and they are the first to melanocortin receptors (especially melanocortin receptor 4 (MCR4)); respond to low levels of circulating leptin. Furthermore, they are the the anorectic peptide α-MSH is an agonist and the orexigenic peptide first to develop leptin resistance in response to a small increase in 708 J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728

PVN LH PBN PVH LH DVM NTS

NTS OC s

Arc t OC n

e Arc r

Vagus nerve e

f f Leptin a

Adipose tissue S

Fuels n i Insulin p CCK s l GLA I a 3V 3V c i v Pancreas Ghrelin r PVH LH LH e Arc C Distension ATP

3V Liver LH Stomach and intestines 3V PVH MCR Arc YR Fig. 2. A diagram of the distributed neural control of ingestive behavior, which involves MCR peripheral detection of signals that come from ingestion of food and the overall disposition POMC of metabolic fuels in the liver, muscle, and adipose tissue. These signals are sent neurally YR CART and hormonally via the caudal hindbrain to relay stations in the mid- and forebrain. Modiﬁed from Schwartz et al., 2000.

NPY AgRP blood leptin concentrations (Olofsson et al., 2013). Changes in ingestive behavior in response to deletion of the gene that encodes NPY, POMC, or AgRP suggests that the most critical neuropeptide for adult appetite and Fuels food intake is AgRP. NPY knockout mice show no effect on body weight or mild obesity, POMC or MCR knockout mice develop obesity, but mice with ablation of the AgRP gene in adulthood starve to death (Cansell et al., 2012; Gropp et al., 2005; Luquet et al., 2005; Segal-Lieberman et al., 2003; Zemel and Shi, 2000). It would be very instructive to know whether these sentinel AgRP cells respond to changes in the availability of oxidizable metabolic fuels. Fig. 3. A diagram of the “arcuate perspective” of control of food intake. The arcuate nucleus of the hypothalamus contains cells that synthesize and secrete orexigenic, anabolic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP) as well as anorectic, cata- Evidence that deemphasizes the arcuate in control of food intake bolic peptides, cocaine and amphetamine-regulated transcript (CART) and alpha- melanocyte-stimulating hormone (α-MSH), the latter being a cleavage product of the Despite the pervasive “arcuate perspective,” the Arc is neither neces- proopiomelanocortin (POMC) gene. According to the arcuate perspective, body weight is regulated because NPY/AgRP and POMC/CART peptides are responsive to gastric signals sary nor sufficient for control of consummatory ingestive behavior and mediated by peripheral hormones such as leptin, ghrelin and/or insulin. energy balance (Grill, 2010). Neonatal ablation of NPY/AgRP Arc cells Modified from Schwartz et al., 2000. in mice fails to disrupt food intake and energy balance at any time during development, and does not prevent hyperphagia that occurs in response to inhibition of glucose oxidation (Luquet et al., 2005, 2007). Neonatal Arc ablation fails to block seasonal changes in food intake and body weight in Siberian hamsters (Ebling et al., 1998). Selective Faulconbridge et al., 2005; Musatov et al., 2007). Metabolic and hor- destruction of AgRP cells in the Arc in adulthood fails to disrupt food in- monal control of consummatory ingestive behavior occurs in chronic take when the lesioned animals are treated with gamma-aminobutyric decerebrate animals, animals in which the communication between acid (GABA) agonists infused directly into the PBN (Wu et al., 2009). the caudal hindbrain and the hypothalamus has been completely sev- Thus, various other peptide networks can modulate food intake, and ered by surgical transection of the brain at the border of the posterior di- these are sufficient to compensate for absence of the Arc when the encephalon and the anterior mesencephalon (reviewed by Grill and ablation occurs early in development or when other peptides are re- Hayes, 2009). Decerebrate and neurologically-intact rats do not differ placed in extra-Arc brain areas. Furthermore, a multitude of hormones significantly in their responses to taste stimuli and hormonal inhibitors affect food intake via actions outside the Arc or even outside the hypo- of ingestive behavior. These experiments provide unequivocal evidence thalamus. Deletion of LepR, estrogen receptor, or treatment with vari- that control of consummatory ingestive behavior can occur without ous orexigenic peptides increases food intake when applied to various descending projections from the hypothalamus, including the Arc extra-Arc regions, to name just a few examples (Dhillon et al., 2006; (reviewed by Grill and Hayes, 2009). J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 709

The neural architecture that provides visceral input to the caudal In the broadest sense, appetitive behaviors are defined as those that hindbrain has been identified, and this network controls food intake bring animals in close contact with a goal, such as food or a potential without input from the forebrain. To be more specific, there is a direct mating partner (Craig, 1917; Everitt, 1990; Lorenz, 1950; Sherrington, neural connection between vagal afferent NTS neurons and the pre- 1906). Appetitive sex behaviors bring animals in contact with oral motor neurons of the parvocellular and intermediate reticular for- opposite-sex conspecifics, and some appetitive sex behaviors induce mation of the hindbrain (Kinzeler and Travers, 2008; Nasse et al., arousal in the potential mating partner (Everitt, 1990; Johnston, 1974, 2008; Travers and Hu, 2000; Travers and Travers, 2007; Travers et al., 1977; Lisk et al., 1983). Appetitive ingestive behaviors bring animals 2010). This pathway is necessary and sufficient for consummatory in close contact with food, and some appetitive ingestive behaviors en- ingestive behavior, i.e., food intake (reviewed by Grill, 2010). By con- sure that energy might be available in the form of a food cache to be trast, the neural architecture connecting the Arc to the motor program eaten during future energetic challenges (Bartness et al., 2011; Vander for chewing and swallowing is still unknown to the best of our Wall, 1990). Appetitive behaviors are partially separable in time and knowledge. space from consummatory behaviors, and those most useful for scientif- One major challenge lies in understanding the integration of the pe- ic study are those that occur hours or days ahead of eating food or cop- ripheral signals with the caudal hindbrain, Arc, and the seemingly end- ulating. Appetitive behaviors precede or follow the final act of less list of chemical messengers known to affect food intake in consummation. Many of these behaviors are easily quantified. In order laboratory rats housed separately with ad libitum access to food. To to gauge hunger motivation, investigators have made use of the fact add to this complexity, functional populations of NPY and melanocortin that hungrier animals are apt to initiate meals sooner, consume an un- receptors reside in extra-hypothalamic and extra-Arc brain areas, and palatable substance, make more effort to gain access to food, and these areas have reciprocal connections to the Arc (Faulconbridge hoard food in their home or burrow. et al., 2005; Grill et al., 1998). From the Arc, NPY/AgRP neurons project The importance of the appetitive-consummatory (motivation- to the paraventricular nucleus of the hypothalamus (PVH), ventromedi- performance) dichotomy lies in the fact that different aspects of al nucleus of the hypothalamus (VMH), dorsomedial nucleus of the hy- ingestive behavior are controlled by different chemical messengers, pothalamus (DMH), and the lateral hypothalamic area (LHA). From acting on different neural substrates, and stimulated by different there cells project to the PBN, NTS, and the dorsomotor nucleus of the environmental stimuli (reviewed by Ball and Balthazart, 2008 with vagus (DMV), areas that control the motor movements of ingestion emphasis on sex behavior). With regard to ingestive behavior, the (reviewed by Zheng et al., 2010). Further complexity is afforded by most obvious example is that consummatory, but not appetitive the dopamine and opiate systems of the nucleus accumbens, ventral ingestive behavior is controlled in the caudal hindbrain (Grill and tegmental area (VTA), and parts of the amygdala. These areas are impli- Kaplan, 1990; Travers et al., 2010). Hormonal and metabolic control cated in control of hunger motivation, learning, reward, reinforcement, of intra-oral food intake remains intact in chronic decerebrate ani- and the willingness to expend effort to gain access to calorically dense mals, though these animals do not approach a food source or engage foods (reviewed by Abizaid, 2009). These areas contain receptors for in operant responding for a food reward (Grill and Hayes, 2009; Grill and detect levels of ghrelin, leptin, and other peripheral hormones and Kaplan, 1990, 1992, 2001, 2002). Another example is that the (reviewed by Abizaid, 2009). brain areas that control predatory hunting differ from those that In summary, ingestive behavior is influenced by a distributed control food intake per unit time. Behaviors such as stalking prey, neural network that encompasses most of the brain and periphery. and approach to food and water, differ from those involved in the The mind boggling array of chemical messengers that influence final killing attack (Waldbillig, 1975). Treatment with the central food intake (Table 1) might suggest multiple, redundant neuroendo- peptide orexin stimulates predatory hunting. Projections from the crine mechanisms, all designed to keep body weight at some opti- periaqueductal gray to lateral hypothalamic orexin cells are critical for mum level. As illustrated in Table 1, however, all of these chemical predatory hunting, although these cells are not necessary for normal messengers have documented effects on reproductive physiology locomotion or food intake (Mota-Ortiz et al., 2012). Another example and/or behavior and other processes not covered by this review. An of the appetitive-consummatory dichotomy occurs with regard to evolutionary perspective suggests that these neuropeptide systems estradiol-induced female sex behavior. In female mice and rats, the were not designed, but rather molded by their link to survival and final, consummatory act of mating, lordosis, is stimulated by sensory reproductive success in environments where energy supply and de- cues from the males and high endogenous levels of estradiol followed mand fluctuated. It might be more productive to focus on how these by progesterone. Lordosis requires classical estradiol action, i.e., estradi- mechanisms influence multiple behaviors, not just food intake, but ol binding to intracellular estrogen receptor-alpha (ER-α), and binding other aspects of ingestion and reproduction. Experiments that in- of the steroid-receptor complex to the estrogen response element (ERE) clude observations of appetitive behaviors suggest that the systems on target genes, which in turn leads to changes in transcription. depicted in Figs. 2 and 3 rank behavioral priorities that optimize Nonclassical estradiol action can potentiate this effect without ERE sig- reproductive success in energetically labile environments. naling, but nonclassical estradiol action is not sufficient for the occur- rence of lordosis (Kow and Pfaff, 2004). Appetitive sex behavior, by Appetitive ingestive behavior contrast, is stimulated by estradiol even in animals that are genetically engineered to lack classical estrogen receptor action. Nonclassical, Historical perspective on appetitive behavior and motivation ERE-independent steroid signaling is sufficient for estradiol-induced appetitive sex behavior whereas classical, ERE-dependent steroid action is Ingestivebehaviorismorecomplexthantheamountoffoodeaten, required for estradiol-induced consummatory sex behavior (McDevitt just as reproductive behavior is more complex than the act of copula- et al., 2008). Similar dissociation between opioidergic mechanisms con- tion. Swallowing food is one final step in a longer sequence of behaviors trolling appetitive and consummatory aspects of sex behavior are seen that determine not only whether an animal will maintain an attractive in quail (Riters et al., 1999). Yet another example of different mechanisms physique, but whether it will survive to reproduce. Appetitive behaviors controlling different aspects of behavior is illustrated by dopaminergic deserve attention because they provide an outward expression of inter- control of incentive vs. the opioidergic control of palatability. The amount nal motivation. We can ask our experimental subjects what they desire of effort an individual will expend to gain access to food is affected by and how much they desire it; but human subjects often lie or exagger- treatments that deplete dopamine in relatively large areas of the nucleus ate, and nonhuman animals often lack the means to describe their accumbens (Mahler and Berridge, 2009; Salamone et al., 2009). Affective motivations to us. Furthermore, appetitive behaviors provide insight facial expressions that occur in response to sweet tastes are stimulated by into mechanisms that alter behavioral priorities. treatments only in very small hedonic “hot spots” in the nucleus 710 J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 accumbens shell and other brain areas (Grill and Norgren, 1978; typically increase their food intake above their normal ad libitum-fed Pfaffmann et al., 1977; Steiner et al., 2001). In nature, incentive, baseline level, and these increases in food intake are as large or larger palatability, appetite, and consumption covary, but in the laboratory, than increases in food hoarding (Hill et al., 1984; Kavaliers and Hirst, they can be dissociated because they are controlled by different neuro- 1986; Zhao and Cao, 2009). Hamsters, voles, and humans, by contrast, peptides and by separate but sometimes overlapping neural circuits. To- respond to energetic challenges with reliable increases in food hoarding gether all of the above studies emphasize different chemical messengers accompanied by little or no increase in food intake. Contrary to popular and different brain areas involved in appetitive and consummatory belief, human beings, unlike laboratory rats and mice, do not reliably behaviors. overeat after a period of fasting (reviewed by Bartness et al., 2011). Some of the more entrenched ideas in the history of ingestive behav- Some investigators reported no post-fast increases in food intake (Al- ior research are difficult to demonstrate. For example, treatments that Hourani and Atoum, 2007; Hetherington et al., 2000; Khatib and modify meal frequency have been thought to control “hunger” and Shafagoj, 2004), whereas others reported only slight increases (20% or have been labeled as “appetitive.” Those that influence the size of less over baseline). People do, however, increase grocery shopping; meals were thought to control “satiety” and labeled as “consummatory” the longer the time since the last meal, the more groceries are pur- (Baird et al., 2006; Blundell, 1986; DiBattista and Sitzer, 1994; Foltin, chased (Beneke and Davis, 1985; Beneke et al., 1988; Dodd et al., 2005; Kowalski et al., 2004; Leibowitz and Alexander, 1991). In rats, 1977; Mela et al., 1996). In humans and hamsters, appetitive aspects consummatory behavior is measured as intraoral intake (voluntary of ingestion, such as food hoarding, are highly sensitive to energetic swallowing of a solution that is directly infused into the oral cavity at challenges and can increase independent of the “consummatory” act an experimenter-determined rate and time of onset). Appetitive behav- of eating. After a period of food deprivation, when food becomes freely ior is measured as the number of approaches to food. Unfortunately, in available, Syrian, Turkish, and Chinese hamsters fail to increase food in- these types of experiments, it is impossible to know where the appeti- take, and Siberian hamsters and Brandt's voles show little or no in- tive behavior ends and the consummatory behavior begins. It is there- creases in food intake (Bartness and Clein, 1994; Bartness et al., 1995; fore difficult to say whether a particular peptide influence motivation, Billington et al., 1984; Rowland, 1982; Silverman and Zucker, 1976). performance, or both. Early investigators argued that NPY affects appe- Rather than compensate for the energy deficits by overeating, these spe- titive not consummatory ingestion because intracerebroventricular cies show massive increases in food hoarding. (ICV) treatment with NPY fails to increase intraoral intake of 0.1 M su- Of these experimental models for the study of appetitive behaviors, crose, although NPY treatment significantly increases the intake of this most progress has been made in the study of food hoarding in Siberian same solution when offered to those rats from a bottle spout (Seeley hamsters, a species with large cheek pouches adapted for carrying food et al., 1995). A reasonable interpretation is that NPY's primary effects (reviewed by Bartness et al., 2011). Increases in food hoarding in are on the appetitive aspects of ingestion, the motivation to go and Siberian hamsters are far greater than increases in food intake in seek food (Ammar et al., 2000, 2005). By contrast, other results show response to food deprivation, diet dilution, lipectomy, treatment with that NPY can decrease or increase intraoral intake. After many years of orexigenic hormones, and neuropeptides including NPY, neuropeptide Y studying this phenomenon, and accounting for repeated experience, receptor 1 (Y1R) agonists, AgRP, and ghrelin (Bartness, 1997; Bartness dose of NPY, age, sex, and species, it appears that NPY increases both ap- and Clein, 1994; Dailey and Bartness, 2008, 2009; Day and Bartness, petitive and consummatory aspects of ingestion (Benoit et al., 2005), 2004; Day et al., 1999, 2005; Keen-Rhinehart and Bartness, 2005, and that intraoral intake and approaches to a bottle of sucrose are of 2007b; Wood and Bartness, 1996, 1997). Food hoarding in Siberian ham- limited value in distinguishing between motivation and performance. sters is decreased by treatment with leptin, CCK, antagonists to the Y1R, If we wish to study the separate neuroendocrine mechanisms for appe- and melanotan II (MT-II), a synthetic analog of α-MSH (Keen-Rhinehart titive and ingestive behaviors, we need to examine behaviors other than and Bartness, 2007a, 2008; Teubner and Bartness, 2010). those directly involved with food or fluid intake. Paradoxically, studying Food hoarding is controlled by neural circuits that differ from those behavior in the more complex natural environment can simplify and that control food intake. Lesions of the Arc attenuate NPY-induced in- clarify the functional significance of the underlying mechanisms. creases in food intake but do not attenuate NPY-induced increases in food hoarding in Siberian hamsters (Dailey and Bartness, 2010). Food Food hoarding intake is increased by treatment with Y5R but not Y1R agonists, whereas food hoarding is increased by treatment with Y1R but not Y5R agonists If we look beyond the consummatory act of eating food, we find em- (Day et al., 2005). In addition, circuits that control food intake are acti- pirical tests of appetitive behavior that are not confounded by the ability vated more rapidly than those that influence food hoarding. Teubner to perform the consummatory behavior. Food hoarding is an appetitive et al. (2012) elegantly exploited this finding to determine which brain behavior characterized by foraging for food and carrying it from the areas are activated concomitant with rapid increases in consummatory source to a home or burrow where it is stored for a period of time before behavior and which were activated concomitant with the slower in- it is consumed (Vander Wall, 1990). In rats, food hoarding is utilized as a creases in appetitive behavior. Food hoarding in Siberian hamsters is proxy for hunger motivation. In these experiments, rats are limited in significantly increased after ICV co-injection of NPY and AgRP at doses the time and amount of food they eat per day, which induces body that are not effective when administered separately. This suggests that weight loss. The experimenter determines the body weight at which NPY and AgRP interact to control food hoarding, possibly at the the rats increase their food hoarding. Using this method, it has been intercellular level. Combined treatment with NPY + AgRP stimulates demonstrated that hunger motivation is decreased by adrenalectomy increases in food intake as early as 1 h after injection, whereas the and corticotropin-releasing hormone (CRH) treatment, and increased same treatment does not increase food hoarding until 4–14 h after in- by food deprivation, housing at cold ambient temperatures, and periph- jection. At the early time point when food intake is elevated, increases eral treatment with low doses of glucocorticoids (Cabanac and Richard, in cellular activation occur in the PVH and perifornical area (PFA). At 1995; Fantino and Cabanac, 1984; Gosselin and Cabanac, 1997; Michel the later time point when hoarding is elevated, increases in cellular and Cabanac, 1999). Food hoarding in rats is not influenced by NPY activation occur in these same areas plus in the central nucleus of the treatment or treatment with high doses of glucocorticoids (Cabanac amygdala (CeA) and the subzona incerta (SZI). Despite the dogma et al., 1997; Michel and Cabanac, 1999). that all changes in ingestive behavior involve the Arc, there is no in- In response to energetic challenges, hamsters increase food hoarding crease in cellular activation in the Arc with co-infusion of subthreshold without increases in food intake. In this regard, human beings (Homo doses of NPY + AgRP that significantly increases food intake and sapiens) share more in common with hamsters than they do with rats hoarding in Siberian hamsters. There are no significant increases in cel- or mice. After a period of fasting or food restriction, rats and mice lular activation in the VMH, Arc, AP, or NTS at either time point. These J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 711 data provide correlational evidence for discrete locations in control of Summary of appetitive behaviors appetitive and consummatory behavior. Specifically, AgRP might have synergistic effects on NPY-induced hoarding in the CeA and SZI The above results in Mongolian gerbils, Brandt's voles, and toads are (Teubner et al., 2012), brain areas with Y1R as well as MC4R receptors consistent with Salamone's ideas derived from studying dopaminergic (Lyons and Thiele, 2010; Vaughan et al., 2011). These data reveal two control of effort in laboratory rats. Salamone explains that dopamine, new brain areas (CeA and SZI) that might be particularly important for acting in the nucleus accumbens, is critical for incentive motivation as hunger motivation and their expression via appetitive behaviors. It measured by the specific appetitive behaviors that reflect the cost an will be interesting to determine the roll of CRH as well as other chemical individual will pay to gain access to a calorically dense, highly palatable messengers that are found in these two brain areas. food (Salamone et al., 2009). In voles, gerbils, and toads, dopamine Food hoarding is an appetitive behavior that might elucidate mech- comes into play when the behaviors involve hoarding, hunting, and anisms involved in the incentive, drive, or motivation to shop for grocer- catching prey: all three appetitive ingestive behaviors that involve ies. Some Mongolian gerbils (Meriones unguiculatus) for instance hoard significant effort to gain access to a highly valued food. Activation of food whereas others never hoard food (nonhoarders), and there are dopamine circuitry is associated with choosing to work harder and lon- interesting differences among these two groups in brain areas involved ger for a highly valued goal, rather than to settle for an easily obtained, in motivation (Yang et al., 2011). The act of hoarding in ad libitum-fed immediately available, less valued goal. By the same line of thinking, gerbils is accompanied by increased cellular activation in the nucleus dopamine depletion is expected to be associated with immediate con- accumbens, VTA, and LHA, particularly in tyrosine hydroxylase (TH)- sumption of a less valued stimulus, as long as little or no effort is containing cells. TH is the rate-limiting enzyme for dopamine conver- required to obtain that stimulus. sion (Yang et al., 2011). Food deprivation increases food hoarding A growing body of evidence documents integration of circuits in- in high-hoarding gerbils, and also in some of the gerbils that were volved in drug addiction, i.e., the mesolimbic dopamine system, with previously classified as nonhoarders. In this latter group of former those involved in the incentive for, and rewarding or reinforcing proper- nonhoarders, food deprivation-induced increases in hoarding do not in- ties of food and sex. The medial preoptic area of the hypothalamus crease cellular activation in the VTA (Yang et al., 2011). Food-deprived (mPOA), which is a brain area critical for sex behavior, also innervates Brandt's voles (Lasiopodomys brandtii) also increase food hoarding the mesolimbic dopamine areas (Tobiansky et al., 2013). Furthermore, when provided the opportunity (Zhang et al., 2011). Both increased lesions of the mPOA augment cocaine-induced conditioned place pref- food hoarding and intake are associated with increases in cellular acti- erence and cellular activation in the mesolimbic dopamine circuit. vation in TH-containing and orexin cells in brain areas including the More than half of the mPOA-VTA efferents are sensitive to dopamine nucleus accumbens and VTA (Zhang et al., 2011). The association be- (Tobiansky et al., 2013). These results illustrate one of many possible in- tween VTA cellular activation in dopaminergic cells and spontaneous, teractions among neural systems that mediate the naturally-rewarding but not food deprivation-induced food hoarding, suggests that the effects of natural stimuli and the systems that mediate the addictive ef- VTA might play a causal role in the motivation or incentive to hoard fects of drugs. It will be interesting to determine whether food hoarding food. Animals with the propensity to hoard food or previous experience in Syrian and Siberian hamsters is also associated with the dopaminer- with food hoarding might be more prone to work for a valued reward, gic system, particularly since NPY infused into the PFA increases food whereas the nonhoarders might be more willing to eat low value food hoarding (Dailey and Bartness, 2009), and natural increases in food in close proximity. This has obvious relevance to our own species mak- hoarding are associated with increases in cellular activation in the SZI ing choices in an environment of food abundance. and CeA (Teubner et al., 2012). In Syrian hamsters, food restriction decreases appetitive sex behavior and increases food hoarding, but the same levels of food Hunting and prey catching restriction does not decrease the rewarding aspects of mating (the ability to condition a place preference with mating as a reinforcer) Dopamine, NPY, and the melanocortins influence hunting and (Lazzarini et al., 1988; Schneider et al., 1988). Food restriction does prey catching, two appetitive behaviors that are separated in time not reverse the mating-induced increases in cellular activation in and space from chewing and swallowing. Investigators studying the mesolimbic dopamine system, but it is not known whether prey catching in anurans have gone so far as to speculate that vaginal scent marking itself is rewarding (without it leading to melanocortins and the HPA (or HPI) system are more important as vagino-cervical stimulation by the male), and, if so, whether food “antipredator” than as anorectic peptides. In the common toad restriction decreases the rewarding aspects of appetitive behavior, (Bufo bufo), for instance, the dopamine agonist, apomorphine, blocks or whether food restriction simply increases the reward value of locomotion and turning toward prey while it promotes snapping in a food (Klingerman et al., 2011a). stationary, sit-and-wait position. These two aspects of ingestion Another gap in our understanding is related to the effects of deficits occur concomitant with increased cellular activation in different in metabolic energy availability on food hoarding. In Siberian and Syrian brain areas. In response to apomorphine treatment, decreased cellu- hamsters, as well as the Mongolian gerbils, food hoarding is increased lar activation occurs in brain areas involved in locomotion and turn- by food deprivation. How is the deficit in energy availability detected, ing toward prey (medial tectum and ventral striatum), whereas what exactly is detected, and where are these detectors? Food intake increased cellular activation occurs in those brain areas involved in in rats is highly responsive to treatments that deplete the availability snapping (medial reticular formation and hypoglossal nucleus). of specific metabolic fuels, whereas food hoarding in hamsters, and Increases are also found in brain areas related to hunger motivation other measures of hunger motivation do not appear to be sensitive to including the nucleus accumbens, ventral tegmentum, ventromedial inhibition of the oxidation of those particular fuels. In rats, food intake pallidum, and septum. These structures are thought to influence mo- is increased by treatments that block either glucose or fatty acid oxida- tivation and reinforcing aspects of snapping in anurans (Ewert et al., tion, and there is a synergistic stimulatory effect when the oxidation of 1999, 2001; Glagow and Ewert, 1994, 1996, 1997a, 1997b, 1999). both fuels are blocked simultaneously (Friedman, 1992; Ritter, 1986). This amphibian example illustrates the adaptive import of appetitive These same treatments fail to influence food hoarding in Siberian ham- behavior. Food deprived toads are more likely to remain active even sters, at least at the range of doses tried so far (Bartness and Clein, in the presence of predators, and thus, they are less likely to survive 1994). This raises the interesting possibility that some appetitive behav- predation than toads that are well fed (Heinen, 1994). These studies iors are controlled by hormones, such as ghrelin and leptin, whereas suggest that the degree of satiety is critical for individual survival in food intake is directly affected by the availability of oxidizable metabolic habitats where there may be predators (from Carr, 2002). fuels (Lazzarini et al., 1988; Schneider et al., 1988). 712 J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728

Do the hormones that influence appetitive ingestive behaviors act as king penguins (Aptenodytes patagonicus) and emperor penguins directly on brain mechanisms that control these behaviors or indirectly (Aptenodytes forsteri), long-term fasting during the breeding season by changing the disposition of metabolic fuels? Is there an interaction can lead to reproductive success, but if internal lipid stores are depleted between fuel availability and the central peptides that control appetitive and parents are forced to dip into their lean mass for gluconeogenesis, behavior? There is precedence for this type of interaction; the resistance the parents abandon their eggs or chicks (Dewasmes et al., 1980; to the action of leptin, insulin and ghrelin on food intake increases Robin et al., 1998; Warham, 1996). Similarly, in equatorial birds such with adiposity (Caro et al., 1996; Cusin et al., 1996; Schwartz et al., as jungle fowl (Gallus gallus) the mothers eat little or nothing while 1996; Ur et al., 1996). Treatment with orexin A increases food intake sitting on their nests full of eggs, losing 20% of their body weight in ad libitum-fed but not food restricted female rats, and treatment during the 20-day incubation (Sherry et al., 1980). In fish, the tradeoff with orexin A inhibits pulsatile LH secretion in food-deprived but not between foraging and courtship is the foundation of many behavioral in ad libitum-fed or food-deprived, glucose-treated female rats (Furuta ecology studies (Abrahams, 1993; Fernald and Hirata, 1977; Griffiths, et al., 2010). In common lizards (Zootoca vivipara), glucocorticoids in- 1996; Lindstrom et al., 2009). African cichlids (e.g., Sarotherodon creased activity and thermoregulatory behaviors in well-fed but not in melanotheron) are normally voracious carnivores, with fish eggs food-deprived males (Cote et al., 2010). In house sparrows (Passer topping their list of favorite foods. After mating, however, males domesticus), glucocorticoid treatment inhibits feeding responses and and females (depending on the species) display remarkable restraint coloration in energetically stressed but not in unstressed chicks by incubating fertilized eggs in their mouths (Goldstein, 1973). (Loiseau et al., 2008). In black-legged kittiwakes (Rissa tridactyla), Mechanisms that inhibit eating are necessary, but the duration of glucocorticoid-induced foraging is stimulated in birds with high levels inhibition is only long enough to allow the individual to get busy with of body weight but inhibited in those in poor condition (low body reproductive activities, i.e., courtship, copulation, or offspring care. It is weight) (Kitaysky et al., 2001). Given the importance of glucocorticoids well established that severe metabolic challenges (e.g., food deprivation and gonadal sex steroids and their interactions with energy availability, in lean animals) inhibit the HPG system, but new insights show that what are their effects on food hoarding? Given the fact that glucocorti- mild energetic challenges (less than 25% restriction in fattened animals) coids control fuel metabolism and storage, it will be important to exam- influence moment-to-moment decisions about whether to engage in ine the behavioral effects when both hormone level and the availability reproductive or ingestive behaviors. Severe energetic challenges inhibit of metabolic fuels are manipulated simultaneously. the HPG system in almost every species in which it has been studied (reviewed by Bronson, 1989; Fernandez-Fernandez et al., 2006; Reasons to stop eating Hill et al., 2008; Schneider et al., 2012; Wade and Jones, 2004; Wade and Schneider, 1992). Mild energetic challenges can inhibit sexual The choice between eating and mating motivation, without significant effects on circulating concentrations of gonadal steroids (Klingerman et al., 2010, 2011a, 2011b; Schneider, It is often assumed that food intake “regulation” functions solely to 2006; Schneider et al., 2007). This has not impressed many laboratory prevent body weight gain, insulin resistance, and obesity. There are, scientists, but it is important in nature, to promote vigilant foraging however, many other good reasons to stop eating. In many species, for- and eating prior to engaging in the energetically costly process of repro- aging and eating are incompatible with courtship, mating, migration, duction, and to avoid wasted efforts on courtship during the infertile and hibernation/torpor, the latter being a regulated drop in body tem- phases of the reproductive cycle. Furthermore, it is important to charac- perature that decreases the energy expenditure required for survival terize effects of mild energetic challenges on behavior because they are during periods of low ambient temperature and food availability. The mediated by so-called anorectic and orexigenic peptides and hormones. focus of this review is the conflict between ingestive behavior and re- It follows that one critical role of ‘satiety’ hormones is to set production, but several excellent reviews indicate that similar mecha- behavioral priorities in order to optimize reproductive success in nisms are at work when ingestive behavior is inhibited during torpor natural habitats where food availability varies unpredictably. This and hibernation (Dark, 2005; Florant and Healy, 2012; Humphries hypothesis is useful because it predicts that the effects of said hor- et al., 2003). mones on ingestive/reproductive behaviors will differ according to Energy acquisition and storage is an important prerequisite for re- 1) the availability of metabolic fuels (energy that can be derived productive success (Bronson, 1989). Thus, in most species, behavioral from food), and 2) the availability of potential mating partners. sequences are organized so that a period of eating and fattening often proceeds mating and caring for offspring. This is particularly important Preference for food or males in Syrian hamsters in habitats where food availability fluctuates or is unpredictable. Bull elephant seals (Miriounga angustirostris) spend several months at sea Work with Syrian hamsters shows that ovarian steroids and GnIH doing little else but fishing, eating, and accumulating massive stores of are likely to be involved in orchestrating behavioral motivation, i.e., blubber. The blubber is critical for reproductive success, because the the disposition of energy availability, GnIH, and ovarian steroids dictate bulls fast for several weeks while they compete for territories. The fast the choice between courtship and food hoarding. continues while the winners of the territorial competitions impregnate Prior to the experiments on Syrian hamsters, it was well known that multiple females (Le Boeuf and Laws, 1994). Fatty acids mobilized from food intake fluctuates over the menstrual cycle in primates, including the triglycerides stored in blubber allow them to make a radical switch women (reviewed by Buffenstein et al., 1995; Fessler, 2003), and over in behavioral priorities: from aquatic foraging to terrestrial territorial the estrous cycle in nonprimates housed in the absence of conspecific defense on beaches miles from their food source. Male fur seals males (reviewed by Asarian and Geary, 2006; Wade, 1972; Wade (Callorhinus ursinus) also fast for several weeks during the breeding sea- and Gray, 1979). The decrease in food intake coincides with the son (Baker et al., 1994; Osgood et al., 1914). Not all examples are as ex- periovulatory peak in plasma estradiol concentrations and the increase treme, however. Red deer stags (Cervus elaphus) reduce food intake and in sexual motivation and/or behavior. Ovariectomy-induced hyperpha- body fat during the rut, even though food is readily available and their gia is reversed by estradiol but not progesterone treatment (reviewed female mating partners continue to eat normally (Mitchell et al., by Asarian and Geary, 2006; Wade, 1972). In women, fluctuations in 1976). Female Syrian hamsters (Mesocricetus auratus) engage in intense food intake over the menstrual cycle are found in some but not all foraging, hoarding, and eating for the three infertile days of their ovula- studies, but in women that restrict their food intake, binge-eating is tory cycle and then neglect their foraging duties for the few short hours less likely during the periovulatory phase of the menstrual cycle that they engage in sex behavior on the eve of the fourth day (Figs. 4 and (Klump et al., 2006). In addition to effects on food intake and energy 5). Examples like these are not confined to mammals. In sea birds, such balance, estradiol is critical for sexual motivation and behavior in J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 713 females of most laboratory species (Drewett, 1973; McDonald and in ambient temperature. Hamsters are expected to have controls that Meyerson, 1973; Meyerson and Lindstrom, 1973; Myerson et al., balance their hunger for food with the need to remain safe from preda- 1973). Estradiol is also important for sexual libido in women. Although tors and harsh environmental conditions. This short, active, above- women can and do have sexual intercourse over the entire menstrual ground time period is likely to be a critical point of conflict between ap- cycle, there are documented increases in sexual motivation, sexual petitive sex and ingestive behaviors. Engaging in courtship behavior fantasy, masturbation, and other aspects of sexuality during the during this 90-minute period might preclude vigilant food hoarding, periovulatory period (Bullivant et al., 2004; Durante and Li, 2009; thereby compromising the females' ability to survive future energy Gangestad, 2001; Gangestad and Thornhill, 2008; Tarin and Gomez- shortages. On the other hand, engaging in food hoarding during the Piquer, 2002). In primates, estradiol is implicated in female sexual de- periovulatory period would likely preclude rendezvous with a potential sire by both menstrual cycle correlations (Roney and Simmons, 2013) mating partner at the burrow entrance. Thus, hamsters are an excellent and experiments that manipulate plasma estradiol concentrations species for testing the hypothesis that so-called “anorectic” or “satiety” (Wallen, 2001). Even in male mice, classical genotropic action, which hormones orchestrate behavioral motivation in environments where involves binding of estradiol to estradiol receptor (ER), is necessary energy availability fluctuates (Klingerman et al., 2010; Schneider et al., for male sex behavior, even in the presence of high circulating testoster- 2007). one concentrations (McDevitt et al., 2007). The entangled mechanisms Hunger motivation in Syrian hamsters is reflected by food hoarding; controlling energy balance and reproduction are illustrated by after a period of food deprivation, Syrian hamsters fail to increase food animals with mutations that lead to a nonfunctional ER-α.ER-α intake (Silverman and Zucker, 1976), but food-deprived hamsters knockout mice lack a functional ER-α, lack estradiol-negative show significant increases in food hoarding, increasing food hoarding feedback on luteinizing hormone (LH) secretion, and develop obesity, ten to a hundred fold (Buckley and Schneider, 2003; Smith and Ross, increased adiposity, decreased energy expenditure, hyperinsulinemia, 1950). Sexual motivation in hamsters is determined by counting the and hyperleptinemia (Heine et al., 2000; Musatov et al., 2007; number of vaginal scent marks made in response to adult male ham- Ohlsson et al., 2000; Rissman et al., 1997). Estradiol-negative feedback, sters or male hamster odors (Johnson, 1973; Johnston, 1974, 1975, appetitive sex behaviors, and all metabolic parameters are rescued by a 1977; Tiefer and Johnson, 1971). Another measure of sexual motivation mutation that restores nonclassical estradiol signaling while simulta- is the females' preference for spending time with either males or food. neously eliminating all classical estradiol action (McDevitt et al., 2008; These appetitive sex and ingestive behaviors are likely to be important Park et al., 2011). Other mutations are designed to eliminate functional to Syrian hamsters in the wild. ER-α specifically in neural cells that synthesize POMC. These mice lack To examine the role of energy availability on the choice between estradiol-negative feedback on LH secretion and are hyperphagic but food and sex, estrous-cycling female hamsters are housed in a burrow show normal body weight and adiposity. Mutations that eliminate ER- system comprised of a home cage, a tunnel leading to a t-shaped inter- α in neurons that synthesize SF-1 result in normal estradiol-negative section, and two more tunnels leading in the opposite directions: one feedback, normal food intake, infertility, and abdominal obesity (Xu tunnel leads to food and the other leads to a sexually-experience male et al., 2011). Together, these data show reproduction and energy bal- hamster. Female subjects are either fed ad libitum or mildly food re- ance remain tightly coupled even when point mutations dissect aspects stricted (75% of ad libitum intake) for 8 days and then tested for of energy balance from one another (e.g., hyperphagia is dissociated 90 min at the onset of the dark phase of the light–dark cycle for food from adiposity). We hypothesize that in natural habitats where animals hoarding and preference for males vs. food. All behaviors and location work hard to forage for their food, this system functions primarily to de- are recorded every 5 s. Food-restricted or ad libitum-fed hamsters are crease the appetite for food and increase the desire for sex in order to tested every day of the estrous cycle to reveal the interaction of gonadal optimize reproductive success. None of the above experiments directly hormones with different energetic and social environments. test the idea that the effects of estradiol on appetitive behaviors have When females are fed ad libitum and provided the choice between been adaptive in environments where energy availability fluctuates. food hoarding and courtship, they prefer courtship over food on every In order to test this hypothesis, environmental energy availability day of the estrous cycle (Klingerman et al., 2010; Schneider et al., must be manipulated and experimental subjects must show quantifi- 2007). In these well-fed females, food hoarding is consistently low able appetitive behaviors. Thus, we measure both appetitive and con- and does not vary much over the estrous cycle. In sharp contrast, summatory behaviors in female Syrian hamsters that have been either when access to a male is coupled with limited energy availability, well-fed or food-restricted prior to behavioral testing. Some experi- females show remarkable fluctuations in food hoarding and preference ments examine gonadally-intact females over the estrous cycle and for males over the estrous cycle (Fig. 4). Food-restricted females show a some examine ovariectomized females treated with either gonadal hor- strong preference for food and high levels of hoarding on the days when mones or vehicle. circulating estradiol is low. Food hoarding falls and vaginal scent mark- Several considerations suggest that attention to the choice between ing increases the night before ovulation and ceases altogether on the food and sex in female Syrian hamsters will provide insight into the night of ovulation (Klingerman et al., 2010). Thus, the effects of estrous mechanisms that orchestrate behavior during energetic challenges. cycle fluctuations in gonadal steroids on appetitive behaviors are Some aspects of hamster behavior (activity, wheel running) are noctur- masked in females with unlimited energy availability. Furthermore, nal in the laboratory, but laboratory-housed Syrian hamsters eat there are no effects of this level of food restriction on consummatory almost as much in the light as in the dark phase of the photoperiod behaviors (lordosis duration and food intake). This is a prime example (Klingerman et al., 2010). In contrast to the laboratory, in their natural of what we miss by studying food intake in animals housed with unlim- habitat near the border of Syria and Turkey, hamsters live separately ited access to food in small cages isolated from conspecifics. in underground burrows and are found to be active only for brief Similar results are seen in ovariectomized females treated with periods at dawn and dusk (Gattermann et al., 2008). Hamsters store physiological levels of ovarian steroids. In ovariectomized females, the massive amounts of food in their burrows, but the sparse distribution fluctuations in appetitive behavior over the estrous cycle are mimicked of the burrow and their large surrounding territories suggests that com- by treatment with estradiol and progesterone, and the effects of estradi- petition for burrows is stiff. Hamsters spend only about 90 min per day ol differ according to energy availability. In unrestricted, estradiol- above ground, and virtually every minute of this time is spent hoarding treated females, the preference for males is high, but not that much food or standing vigilantly at the burrow entrance (Gattermann et al., higher than that of ovariectomized females. Mild food restriction drasti- 2008). This suggests that their nocturnal active period might be cally decreases preference for males (but not lordosis duration) and constricted in the wild by predators or other unknown factors, and increases food hoarding (but not food intake) in ovariectomized but that the burrow provides protection from predators and fluctuations not in estradiol-treated females. Severe food restriction (12–16 days), 714 J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728

Fig. 4. Appetitive sex behavior was measured over the estrous cycle in females either fed ad libitum or food restricted. The Y-axis is male preference, that is, the mean preference for spending time with a male calculated as the time spent with a male divided by (the time spent with a male + the time spent with food) in a 15 min test. Male preference was measured at the onset of the dark period on every day of the estrous cycle in females that were either fed ad libitum or previously food restricted to 75% of their ad libitum intake. In the figures above the graphs, energy availability is symbolized as water filling the large reservoir that provides fuels for all physiological process. Food intake is symbolized as a faucet, and body fat stores are symbolized as the small container on the left of the large reservoir. When energy in the environment is unlimited and energy expenditure requirements are low, there is sufficient energy for sexual motivation, the HPG system, as well as for all of the energy-using processes necessary for survival (top left). However, processes necessary for survival have the first priority. When there are severe metabolic challenges, and females deplete their body fat reserves, there is not enough energy available for the HPG system and sex behavior (not shown). As shown in the picture and graph on the right, after mild energetic challenges that do not inhibit the HPG system, sexual motivation is low on most days of the estrous cycle, however, there is a significant increase in sexual motivation in the periovulatory period when plasma estradiol concentrations are high. As shown in the graph and figure on the left, this estrous cycle fluctuation is masked in hamsters that are housed with food available ad libitum. Modified from Klingerman et al., 2010. unlike mild food restriction, inhibits the preference for males as well as lordosis duration even in females treated with estrous-inducing doses of estradiol and progesterone (Klingerman et al., 2010). These experiments also examine the relative importance of time constraints vs. energy constraints. In the 8 days prior to testing for the choice between food and sex, one group of female hamsters had unlimited time to forage for and hoard food, but overnight food supply was limited to 75% of ad libitum intake. Another group had only limited time each day to forage for and hoard food, but had unlimited energy availability. This latter group did not differ significantly from ad libitum-fed, ad libitum-time controls in their appetitive sex and ingestive behavior, whereas those with limited energy availability showed remarkable fluctuations in food hoarding, vaginal scent marking, and preference for males over the estrous cycle (Klingerman et al., 2010). These results suggest that the hamsters' behavioral priorities are pro- foundly affected by their experience with limited energy availability Fig. 5. Appetitive ingestive behavior was measured over the estrous cycle in females fed ad but not by their experience with limited time for foraging and hoarding. libitum or food restricted. The Y axis is grams of food hoarded in a 90 min test at the onset of the dark period on every day of the estrous cycle in females that were either fed ad libitum These results are consistent with the idea that the hormones of the (solid line, filled circles) or previously food restricted to 75% of their ad libitum intake (dashed estrous cycle modulate appetitive ingestive and sex behaviors according line, open triangles). After this mild energetic challenge, which did not inhibit the HPG system, to the availability of energy and potential mates. Appetitive behaviors food hoarding was high on most days of the estrous cycle, but decreased as ovulation are affected at low levels of food restriction that have no effect on con- approached and was at its nadir on the day of estrus (dashed line, open triangles). This estrous cycle fluctuation in appetitive ingestive behavior is masked in hamsters that are housed with summatory behaviors. This role of estradiol is obscured in most labora- food available ad libitum (solid line, filled circles). Above the time points for mean food tories because appetitive behaviors are ignored, food intake is measured hoarded, hamster appetitive sex behaviors are depicted. On days 1 and 2, the post-ovulatory in females isolated from males and under conditions of artificial energy day, and the early follicular phase, hamsters show very few appetitive sex behaviors. On the abundance and minimal energy demands. In environments where ener- third day of the estrous cycle, the day before ovulation, females show peak levels of vaginal gy availability fluctuates or is unpredictable, an important function of scent marking. On the fourth day, the day of ovulation,femalesshowlordosisinresponseto a sexually-experienced, adult male hamster. anorectic gonadal hormones is to promote vigilant food hoarding and Modified from Klingerman et al., 2010. prevent sexual adventures during the nonfertile phases of the estrous J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 715 cycle. Under conditions of constant energy abundance, however, sexual The choice between food and sex in other species motivation remains high despite fluctuations in gonadal hormones (Figs. 4 and 5). This phenomenon, energetic control of appetitive sex and ingestive GnIH, NPY, leptin, and their interaction with ovarian steroid recep- behavior, is echoed in other vertebrate species. We have already tors are implicated in energetic control of appetitive behaviors. First, noted that in Siberian hamsters, appetitive ingestive behaviors are ICV treatment with GnIH mimics the effect of mild food restriction by more sensitive than consummatory behaviors to NPY, leptin, ghrelin, inhibiting appetitive, but not consummatory aspects of sex behavior in melanocortins, and CCK (reviewed by Bartness et al., 2011). Even in female Syrian hamsters (Piekarski et al., 2012). In an experiment rats, NPY treatment increases the number of approaches to a bottle of designed to discriminate among GnIH effects on appetitive behavior, sucrose, an empty bottle, or a bottle of water at doses that do not consummatory behavior, or the HPG system, GnIH is implicated in increase (and might sometimes decrease) consummatory behavior only appetitive behavior. Cellular activation in GnIH cells in food- (Ammar et al., 2000). The lack of NPY effects on consummatory behav- deprived, lean, anestrous hamsters was compared to that in food- ior in some experiments can be explained by the effects of repeated deprived, fat, estrous-cycling hamsters. Cellular activation in GnIH testing or other confounds (Benoit et al., 2005). More robust, however, cells was elevated in both food-deprived groups, and did not differ are the effects of NPY and leptin in the presence of opposite-sex conspe- between food-deprived, anestrous compared to food-deprived, estrous cifics. Increases in response to NPY and decreases in response to leptin cycling hamsters. In hamsters subjected to mild food restriction, cellular in appetitive ingestive behaviors are consistent with their role in or- activation in GnIH cells was closely associated with fluctuations in vaginal chestrating the appetites for food and sex (Ammar et al., 2005; scent marking, the preference for spending time with males, and food Bartness et al., 2011; Schneider et al., 2007; Sederholm et al., 2002; hoarding (Klingerman et al., 2011b). Together, the above results illustrate Seeley et al., 1995). Well-fed male rats offered a choice between an that the effects of hormones and neuropeptides vary with energy avail- estrous female and a bottle of sucrose will choose the female every ability. GnIH function is more closely related to behavioral motivation time. By contrast, NPY-treated males offered a choice between an than to control of consummatory behavior and the HPG system. estrous female and a bottle of sucrose show a bias toward the sucrose so- Furthermore, vaginal scent marking is inhibited by 24 h of food lution. Leptin-treated males offered a choice between sugar solution and deprivation and the effects of food deprivation are reversed by treat- sex with an estrous female decrease their frequency of approaches to a ment with leptin (Schneider et al., 2007), known to inhibit effects of bottle of sucrose and consume fewer calories overall, but they also in- NPY (Kotz et al., 1998). The effects of leptin on vaginal scent marking crease the frequency of ejaculations relative to vehicle-treated control (an appetitive sex behavior) was greater in fattened, fasted females males (Ammar et al., 2000). These results concur with our hamster stud- (that continued to show estrous cycles and high levels of ovarian ste- ies demonstrating that NPY and leptin are more than simply orexigenic roids) than in ad libitum-fed females. In another experiment by W. P. and anorectic; they direct attention toward or away from sexual stimuli. Williams in the Kriegsfeld laboratory, fibers that contain NPY are The results of Klingerman et al. (2010, 2012) in Syrian hamsters found in close apposition to GnIH cells in the Syrian hamster DMH demonstrate that appetitive behaviors respond to gonadal steroids dif- (Klingerman et al., 2011b). ferently, depending on the energetic status of the female (prior food re- It is important to note that effects of mild food restriction occur striction or ad libitum feeding). A similar interaction between prior without effects on circulating gonadal steroids. In support of the idea energetic status and behavioral response to hormones is seen in at that energetic challenges influence sensitivity to ovarian steroids, ener- least three other independent laboratories studying food-restricted getic challenges decrease levels of estrogen receptor-alpha (ER-α)in male rats. In male hooded Wistar rats, the latency to intromission was the VMH (implicated in sex behavior) and increase levels of ER-α in the significantly longer in those food restricted by 50% compared to those PVH (Li et al., 1994). In support of a role for both NPY and CRH in hamster restricted by 25% or 0%, and females preferred ad libitum-fed males motivation, central treatment with either a Y2/5 R agonist or a CRH over the 50% food-restricted males, even though there was no signifi- receptor antagonist reverses the effects of severe food deprivation on cant difference among the two levels of restriction in plasma testoster- lordosis duration (Jones et al., 2002, 2004; Keene et al., 2003; Seymour one concentrations (Govic et al., 2008). In another study using male et al., 2005). Although this latter study focused on lordosis duration, not Wister rats, food restriction significantly decreased mount and intro- the appetitive behavior vaginal scent marking, the results are consistent mission latency without significant effect on plasma testosterone with a role for NPY and CRH on the underlying sexual motivation. (Alvarenga et al., 2009). In yet another study of male laboratory rats, Consistent with these studies on appetitive behavior, other investi- food restriction accelerated the disappearance of copulatory behavior gators have suggested that GnIH is important for consummatory aspects that normally accompanies castration (Broere et al., 1985). All of these of ingestive behavior and for control of the HPG system. Clarke et al., studies are consistent with the idea that male copulatory motivation have noted that central GnIH treatment increases food intake while it and performance are inhibited by energetic challenges. They are all con- inhibits the HPG system in mice, rats, sheep, and monkeys (Clarke sistent with the idea that this occurs via decreases in behavioral respon- et al., 2012). These results are not in conflict with GnIH effects on moti- siveness to gonadal steroids. vation; these investigators did not attempt to differentiate between Similarly, in male mice, appetitive sex behavior can be measured as appetitive and consummatory behavior. Our studies in Syrian hamsters rapid, short latency courtship ultrasounds in response to female mice indicate that GnIH is more closely associated with appetitive than con- and their odors, and this appetitive behavior is prevented by pretreat- summatory sex and ingestive behavior (Klingerman et al., 2011b). ment with ghrelin (Shah and Nyby, 2010), an orexigenic gut hormone This line of research suggests that when animals are mildly energet- that acts via AgRP/NPY. Male mouse ultrasounds are testosterone- ically challenged, sexual motivation is inhibited by orexigenic peptides dependent (Sipos and Nyby, 1998), but the effects of ghrelin occur with- that promote vigilant foraging and hoarding during the infertile part in 20 min, more rapid than would be expected if they occurred via inhi- of the estrous cycle. As ovulation nears, however, the effects of these bition of the HPG system and via inhibition of testosterone secretion orexigenic peptides are inhibited by rising levels of estradiol. Estradiol (Shah and Nyby, 2010). Together, these results are consistent with the dampens the urge to forage and turns attention toward sex; perhaps hypothesis that one important function of putative “body weight- via effects on anorectic peptides. This idea is supported by data showing regulating” hormones is to orchestrate the motivation for foraging and the expected interaction between estradiol and other hormones, includ- courting on a moment-to-moment basis. The effects of food deprivation ing corticosteroids, ghrelin, the melanocortins, and CCK (Asarian and or restriction was not examined, but ghrelin is known to increase in Geary, 2007; Clegg et al., 2007; Gao et al., 2007). Thus, future work food-deprived rodents (Gualillo et al., 2002), and thus, these experi- should be aimed at understanding the role of other neuropeptide sys- ment implicate ghrelin in energetic effects on male appetitive sex tems, such as the CRH system, in setting behavioral priorities. behavior. 716 J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728

Food deprivation inhibits some aspects of sex behavior in female start of infusion and stimulates food intake at 4–5handreturnsto meadow voles (Microtus pennsylvanicus), and there are some differ- baseline at 24 h after infusion (Morris and Crews, 1990). Further- ences in this species from the examples discussed thus far. The effects more, the switch from a preference for sex to a preference for food of deprivation are limited to attractivity. The scent marks of female is associated with fluctuations in plasma glucocorticoids and mela- meadow voles are attractive to males such that males show a preference tonin. Treatment with corticosterone, melatonin, or serotonergic for female versus male scent marks, and food deprivation of females type 2A receptor antagonist during the breeding season suppresses decreases the male's preference for those marks (Pierce and Ferkin, courtship in male red-sided garter snakes in a dose-dependent 2005; Pierce et al., 2005). Food deprivation also inhibits self grooming manner, whereas treatment with glucocorticoid synthesis inhibitors in both sexes, an appetitive behavior that releases volatile pheromones increases the preference for food over male pheromones in this into the atmosphere (Hobbs et al., 2012). In contrast the appetitive be- species (Lutterschmidt et al., 2004, 2011). haviors, scent marking and scent overmarking, are not affected by food Corticosterone is inhibitory for reproductive behaviors in many dif- deprivation. Unlike appetitive sex behaviors in Syrian hamsters, ferent species, but a number of species that breed in harsh environ- attractivity of meadow vole scent marks is associated with significant ments appear “resistant” to these effects. This difference might be decreases in plasma estradiol and the effects of food deprivation on related to environmental energy availability. Newly emerged male attractivity are reversed by estradiol treatment (Pierce et al., 2007). red-sided garter snakes trapped near the dens and are about to embark Re-feeding restores attractivity, but it is not necessary for the food- on frenzied courtship and mating have higher circulating concentra- deprived voles to regain their lost body weight (Pierce and Ferkin, tions of corticosterone and a blunted stress response compared to 2005). Together, these results suggest that steroid-dependent phero- those males that have courted and initiated their dispersal to the feed- mone production is sensitive to minute-to-minute changes in circulating grounds. Together, these results suggest that one important role of ing metabolic fuels, rather than signals from body fat content or size. seasonal fluctuations in the stress response is to increase baseline corti- This hypothesis was elegantly supported by experiments in which costerone concentrations while inhibiting the flight-or-fight response in red-sided garter snakes (Thamnophis sirtalis parietalis) were tested in order to promote synchronized mass mating in the spring (Cease et al., an environment that offered the choice between sexual or food- 2007). Thus, newly emergent snakes might benefit from high baseline related stimuli (O'Donnell et al., 2004). In northern-most members of corticosterone concentrations (because corticosterone increases lipoly- this species, males and females must eat enough food to survive an sis, decreases lipogenesis, and increases gluconeogenesis resulting in el- 8 month hibernation period followed by 2–4 weeks of intense court- evated availability of oxidizable fuels). At the same time they would be ship and mating, followed by a new cycle of dispersal, foraging and eat- spared the stress-induced inhibition of sex behavior and the HPG ing (Gregory, 1977). Breeding and eating are thought to be mutually system. It would be interesting to know whether high circulating levels exclusive in the wild because courting males at the dens are found rare- of glucocorticoids would support breeding even in severely undernour- ly if ever with food in their stomachs (Aleksiuk and Gregory, 1974; ished snakes. Aleksiuk and Stewart, 1971; Crews et al., 1987) and males have been We speculate that the switch from courtship to foraging behavior known to refuse food offered by the experimenter during the breeding might be related to the need to replenish depleted stores of metabolic season (Aleksiuk and Gregory, 1974; Crews et al., 1987). O'Donnell fuels after two weeks of intense energy expenditure (mating) and/or et al. asked whether newly emerged, breeding snakes have a normal ap- post-hibernation changes in thermoregulatory function. One hypothesis petite and are able to eat, or whether there is an endogenous mecha- is that the trigger for increased feeding results from an interaction be- nism that inhibits food intake while courting and mating. tween high levels of glucocorticoids and a depleted supply of metabolic In this ingenious design, male red-sided garter snakes are tested in a fuels (glucose, free fatty acids, or ketone bodies) or accompanying low Y-maze that offers olfactory cues from either a prey item or sexually levels of hormones such as leptin and high levels of hormones such as attractive females (females in which the attractiveness pheromone is ghrelin. Changes in internally circulating oxidizable fuels might not be present). Red-sided garter snakes use chemical trails to locate prey reflected in overall body weight or condition. As with the Syrian ham- items such as earthworms (Halpern and Martínez-Marcos, 2003; sters discussed above, steroid effects on behavior may differ according Halpern et al., 1986; Kubie and Halpern, 1975), and males use chemical to internal metabolic fuel availability. This is a testable hypothesis. trails to locate potential mates (e.g., see LeMaster and Mason, 2001, The switch from mating to eating has been linked to the HPA system 2002; Mason et al., 1989, 1990). Thus, in the preference test, the male and metabolism in northern sea birds that cope with cold winters. Ant- is placed in the starting position at the outer arm of the Y, and the exper- arctic king penguins (Aptenodytes patagonicus) fast for up to one month imenter records the male's preferences and behaviors when provided while mating, incubating, and molting (Cherel et al., 1988). During incu- with two types of odor trails. After the Y-maze test, courtship and eating bation, one parent fasts and incubates, while the other forages for food are assessed directly, by exposing males to females in the absence of far out at sea. These shifts in ingestive behavior are accompanied by dis- food, or exposing males to prey in the absence of females, and scoring tinct and quantifiable appetitive behaviors. Just before egg abandon- their responses (O'Donnell et al., 2004). ment, the incubating parent begins to increase locomotor behaviors Male red-sided garter snakes, captured near the den where they and starts singing; the song calls the other parent to the nest, and emerge from hibernation, invariably prefer the arm scented with the these changes in appetitive behavior are correlated with the shift from female pheromone over the arm scented with the food odors, and this utilization of lipid-derived to protein-derived fuels (Groscolas et al., preference is gradually reversed over the next 2–4weeks,untilfinally, 2000). Examination of these appetitive behaviors in the laboratory sug- all males reverse their preference. In post-tests with each stimulus gests that the likelihood of abandonment of either an egg or a chick are alone, the decrease in hunger motivation occurs in the absence of linked to increased plasma concentrations of corticosterone and de- female pheromones. Similarly, the decrease in courtship and mating creased plasma prolactin (Groscolas et al., 2008). Similarly, in emperor occurs in the absence of food and in the presence of females. Thus, the penguins, during the first two phases of fasting, energy for reproduction changes in motivation and appetitive behaviors are due to endogenous is supplied by glycogen and lipid but not protein stores. Glycogenolysis mechanisms that control hunger and sexual motivation. It will be fasci- and lipolysis are stimulated in part by steady concentrations of gluco- nating to find the environmental cues (ambient temperature, photope- corticoids (corticosterone). When lipids are depleted, elevated cortico- riod, energy availability) and endocrine events that determine these sterone and glucagon concentrations trigger gluconeogenesis, creating preferences (O'Donnell et al., 2004). new glucose from amino acids and glycerol, resulting in the breakdown NPY and glucocorticoids are implicated in these changes in the of proteins and muscle wasting. The combination of elevated glucocor- preference for food or sex. ICV treatment with NPY significantly ticoids and low energy availability can be such a powerful motivational inhibits red-sided garter snake courtship behaviors 4–5hafterthe signal that it sometimes causes the birds to abandon the eggs in order to J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 717 forage for food. During fasting, body weight and concentrations of uric response,” but instead remain on the food source as though they are acid and corticosterone increase, whereas plasma levels of beta- food deprived. The biochemical pathways that determine whether a hydroxybutyrate decreases. Decreases in the ketone body, beta- young nematode develops into an adult male or a hermaphrodite hydroxybutyrate, are diagnostic for the depletion of fat fuels because might also determine the appetitive behavior, the “leaving response” ketone bodies are a byproduct of fatty acid oxidation (Robin et al., to a food source (Lipton et al., 2004). Together these results are consis- 1998). Thus, the switch from reproductive to ingestive behavior is not tent with the idea that sex hormones and neuropeptides orchestrate the a simple function of plasma glucocorticoid concentrations, but perhaps choice between food and sex in some of the earliest animals. a function of the ratio of fuel availability to plasma glucocorticoids. This is a testable hypothesis but requires experimental manipulation of ener- Courtship and eating in semelparous species gy availability. This general idea is echoed in at least some species of mammals Not all species curtail reproduction when energy availability is low, and birds that hibernate, species that optimize reproductive success but in these cases, the exception proves the rule: Mechanisms that in environments where fluctuations in energy supply and demand orchestrate the appetites function to optimize reproductive success. In are extreme. Hibernators prepare for winter by increasing their electric fish, (Brachyhypopomus gauderio), males emit an electric organ food intake and body fat storage in the summer and late autumn. In discharge (EOD) that is testosterone-dependent, energetically expen- winter they cease their foraging while they undergo a controlled sive, and necessary for successful competition for female mating part- drop in body temperature. Given the geographic location of hiberna- ners. In the presence of other males, the social competition stimulates tors, the function of hibernation is to conserve metabolic fuels neces- androgen and cortisol secretion, which in turn amplifies the EOD sary for survival during harsh winters when food supplies are (Salazar and Stoddard, 2009). By contrast to other species in which virtually non-existent and ambient temperatures are low. Fattening food restriction inhibits sex behavior, in competing electric fish, EOD is over the summer and early autumn are correlated with increases in amplified by food restriction. Previously food-restricted males that glucocorticoids (Nunes et al., 2006), but there are very few experi- show the strongest EODs will eat more if food is made available, but in ments in which corticosteroids were administered to determine the absence of food, they amplify the EODs and rapidly burn through their effects on body temperature, torpor, or hibernation. Other in- their remaining energy reserves (Gavassa and Stoddard, 2012). The vestigators, however, manipulated corticosteroid levels in hibernat- difference between electric fish and species that delay reproduction ing birds. Corticosterone treatment increases nocturnal restfulness until energy becomes available is that electric fish are semelparous. in captive white-crowned sparrows (Buttemer et al., 1991)andin- They get only one chance to mate in their lifetime. The delay of court- creases the incidence of daily torpor in humming birds (Hiebert ship and mating would be for naught; by that time they will be dead. et al., 2000). Furthermore there is some evidence that the effects of The same strategy is seen in other species with severely limited mat- corticosteroids on activity and body temperature differ according ing opportunities. Male Arctic ground squirrels hibernate for 7 winter to energetic history and possibly the availability of metabolic fuels months, and emerge in the spring, in time for what is likely to be their (Hiebert et al., 2000). Missing from studies of glucocorticoids and hi- only chance at becoming a father. Copulation is the prize for surviving bernation is simultaneous manipulation of energy stores, food in- the brutal, two-week, male–male competition. At emergence and take, and glucocorticoid levels. throughout the two weeks of fighting and mating, the males' plasma It is reasonable to imagine that motivation is a unique characteristic cortisol concentrations are at their annual peak and free cortisol is con- of “higher” organisms, and yet motivational priorities are affected by en- stant. Yet, when challenged by another male, testosterone and aggres- ergy availability even in invertebrates with relatively simple nervous sion levels “rise to the occasion” (Boonstra et al., 2001). Only about systems. For example, male nematodes of the species Caenorhabditis one half of the males will survive to the next year, and Boonstra et al. elegans show appetitive behaviors that indicate their interest in either (2001) suggest that this severely limits their lifetime reproductive suc- food or sex, though the nervous system is comprised of only a few cess. The short breeding season, with only one opportunity to mate im- hundred cells (Lipton et al., 2004). Much like the male preference test mediately after hibernation, may have selected for animals that are we use to examine sexual motivation in female hamsters, appetitive buffered from chronic stress incurred by aggression. By contrast, female sex behavior in male C. elegans is quantified by placing males on their hamsters and other rodents are likely to have several opportunities to preferred food source and then measuring how often they exit in search mate, due to their short gestation period (16–18 days) and, in some of mating partners in what the experimenters call a “leaving assay.” species, a postpartum estrous. Thus, despite their short life spans, mul- Leaving a food source in male C. elegans occurs only in a sexual context, tiple litters per season in most small rodents increase the likelihood i.e., it occurs only in adult, gonadally intact males, not in juveniles or cas- that metabolic control of reproduction will have a payoff in terms of trated males. Sexually mature males tend to linger on the food source overall reproductive success. A similar strategy to the semelparous arc- when dining with a potential mating partner (in C. elegans males mate tic ground squirrel is seen in other truly semelparous species (Bradley et with hermaphrodites) but leave readily when no hermaphrodites are al., 1980). In those rotifer species that reproduce only once in a lifetime, present at the food source. Instead, they wander off searching for egg production increases, rather than decreases during starvation (Kirk, mates, but not just any mate; a hermaphrodite with an abundant food 1997). In iteroparous rotifer species, reproduction is delayed by starva- source. These motivated behaviors are sensitive to energy availability. tion, and these species are able to survive starvation longer than the Food-deprived males have a longer latency to leave a food source before semelparous rotifer species. finally exiting the food source in search of a mating partner. The longer In summary, species that will have multiple chances to reproduce in the food deprivation, the longer the males delay their exit from a food their lifetime, delay reproduction under energetic challenges. In species source. These changes in the hunger for food and desire for sex may that will get only one chance to reproduce in their lifetime, energetic be mediated by neuropeptides and sex hormones. Serotonin is released challenges stimulate rather than inhibit reproduction. A testable hy- in response to eating in C. elegans, and mutations in the genes that pothesis is that, in iteroparous species, sensitivity to energetic chal- encode serotonin receptors create males that 1) are insensitive to sero- lenges decreases as animals age and approach reproductive senescence. tonin action and 2) act as though they have been food deprived. They fail to leave a food source in search of mating partners. Mutations or Energy availability and the HPG system other manipulations that inhibit gonadal function also mimic food deprivation, i.e., they prevent males from exiting is search of hermaphro- The study of gradual changes in appetitive behavior under mild, dites. Mutation of the fog-1 gene transformed males that produce temporary energetic challenges on behavioral motivation is relatively sperm into males that produce oocytes, fail to show the “leaving new compared to the well-known effects of metabolic fuel availability 718 J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 on food intake (Friedman, 1989; Ritter, 1986), and the effects of severe It may be true that some laboratory strains of rodents appear to be metabolic challenges on the HPG system (reviewed extensively Crown buffered from the effects of food restriction or deprivation (Jarmon et al., 2007; Elias and Purohit, 2013; Schneider, 2004; Schneider and and Gerall, 1961; Sachs, 1965). This might be due to using animals of a Watts, 2009; Schneider et al., 2012; Wade and Jones, 2004). It has very high initial body fat content, which tends to be true of laboratory long been known that energy is the most important factor that controls vs. wild animals, or it might be an artifact of domestication. In many reproduction in all vertebrate taxa (Bronson, 1989; Gittleman and wild species, the male HPG system is quite sensitive to deficits in energy Thompson, 1988; Lack, 1954; Rousseau and Dufour, 2007; Sibly et al., availability, and these effects are exacerbated in young, lean, peripu- 2012). Both the mechanisms that control the HPG system and those bertal animals (reviewed by Bronson, 1989). For example, mild food re- that control food intake are sensitive to fluctuations in the availability striction results in profound reductions in spermatogenesis, plasma LH, of oxidizable metabolic fuels. Food intake is increased by food restriction and testosterone in deer mice (Peromyscus maniculatus), yet the same or deprivation, and by treatments that decrease levels of glucose oxida- level of food restriction fails to affect the same parameters in house tion, fatty acid oxidation, suppression of hepatic ATP levels, central acti- mice (M. musculus)(Blank and Desjardins, 1985). Male Siberian ham- vation of adenosine monophosphate-activated protein kinase (AMPK), sters are sensitive to very mild food restriction in spring, at the time of enhanced expression of malonyl coenzyme A decarboxylase, and in- the vernal reproductive recrudescence (Dooley and Prendergast, creases in energy expenditure (Friedman, 1989, 1998, 2008; Friedman 2012). Ad libitum-fed males decrease their food intake and become et al., 1986, 1999; He et al., 2006; Horn et al., 2004; Ji and Friedman, gonadally regressed in response to the short day lengths of autumn 1999; Ji et al., 2000; Kohno et al., 2011; Li et al., 2011; Ritter, 1986). Sim- and increase their food intake and show spontaneous gonadal recrudes- ilarly, energetic challenges (e.g., food restriction or deprivation) inhibit cence in the spring. By contrast, males limited to their winter food the HPG system in representative members of every mammalian intake remain gonadally-regressed in spring until such time as they order and of every vertebrate class (reviewed by Bronson, 1989). Fertil- are allowed to increase their food intake (Dooley and Prendergast, ity is constrained by energy availability in birds, reptiles, amphibians, 2012). In early spring when day lengths are increasing and late sum- and fish (Rousseau and Dufour, 2007). Energy availability has well- mer when day lengths are decreasing, Siberian hamsters experience documented inhibitory effects on the HPG system in birds, affecting intermediate day lengths, e.g., 13.5 h of light (10.5 h of dark). In sex, parental, and social behaviors (Lack, 1968; Perfito et al., 2008; intermediate day lengths, the male reproductive system is more Scheuerlein and Gwinner, 2002; Sibly et al., 2012; Thomas et al., 2001; sensitive to food availability than that of males housed in long Watts and Hahn, 2012). Reproductive success is linked to both food days. Food restriction rapidly and significantly decreases body availability and body size in snakes (Shine, 2003; Shine et al., 2000). weight, epididymal white adipose tissue weight, and testes size in Energy availability is linked to reproductive success in amphibians. In hamsters housed in an intermediate day length (13.5 h of light). anurans, reproduction is energetically expensive; females produce The same level of food restriction has no significant effect on these several thousand eggs in a season. Egg size and number in bull frogs parameters in long day-housed males (16 h of light), and intermedi- (Hoplobatrachus tigerinus,formerlyknownasRana tigrina)iscontrolled ate day length has no effect on these parameters in ad libitum-fed by the overall availability of fuels from the diet and body fat stores, and males (Paul et al., 2009a, 2009b). the inhibitory effects of lipectomy on fertility are prevented by increas- As the above examples illustrate, the male reproductive system is ing the frequency of meals (Girish and Saidapur, 2000). Energy avail- clearly responsive to energy deficits, but the effects can be masked by ability is an important mediator of reproductive success in fish. other environmental variables (stimulatory photoperiods, a high body Female zebrafish (Danio rerio) spawn daily when supplied with food, fat content, strong cues from opposite-sex conspecifics). It is difficult but unless they can eat continuously their egg production declines to accurately claim that males of a particular species are less sensitive sharply (Wang et al., 2006). Even in invertebrates, energy availability is to energetic deficits than females if that species has been domesticated linked to reproductive success. Male fiddler crab (Uca lactea)courtship for many generations, selected for maximum reproductive output displays are linked to environmental energy availability; supplementing rather than for the ability to modulate reproductive output according the males' food supply increases the number of nights they engage to energy availability, and tested in only the conditions that are the in courtship displays (Kim et al., 2008). In the fruit fly, (Drosophila most stimulatory for the HPG system (i.e., long days, high levels of melanogaster), females match the rate of re-matings to the perceived body fat storage, ad libitum food intake, strong pheromonal cues from nutritional environment (Wigby et al., 2011). Even in C. elegans, food- opposite-sex conspecifics) (Bronson, 1989; Paul et al., 2009a, 2009b). deprivation inhibits mating and causes retention of eggs, and mating It might be expected that the sensitivity to energy availability varies and egg-laying are stimulated by re-feeding (Luedtke et al., 2010). with age, prior body fat content, and prior energetic challenges, and According to parental investment theory (Trivers, 1972), it might be therefore these factors confound differences due to sex. Parental invest- expected that the male HPG system is insensitive to energy availability, ment theory might underestimate the cost of male reproductive activi- since sperm production requires less energetic investment than oogen- ties. In reality, reproductive success in males is linked to many activities esis, pregnancy, and laction/incubation. To the contrary, deficits in food that include territorial defense, courtship displays, competition for cop- availability inhibit GnRH and luteinizing hormone (LH) secretion in ulations, copulation itself, and, in some cases, parental care. Each of both males and females, and there is a similar pattern in both sexes. In these individual behaviors is not particularly energetically expensive, both males and females, food restriction is a potent inhibitor of LH but the summation of the energy used in these activities may make up secretion even though it has little or no effect on follicle stimulating a substantial portion of the energy budget. Furthermore, whereas hormone (FSH) secretion (e.g., Howland, 1975; Meredith et al., 1986; spermatogenesis is not energetically costly, synthesis and secretion of Root et al., 1975; Sisk and Bronson, 1986). Steroidogenesis in both the ejaculate is more costly, and in some species each ejaculation males and females require pulsatile LH secretion of the amplitude and decreases the sperm count in subsequent ejaculations; thus, energy frequency characteristic of the well-fed animal, and thus, in both and lifetime reproductive success are linked in males (Dewsbury, 1982). sexes, steroidogenesis is quite susceptible to food restriction or depriva- Almost every hormone and neuropeptide that inhibits the HPG sys- tion. Despite these similarities between males and females, male fertility tem increases food intake, whereas almost every hormone and neuro- is less sensitive to energetic challenges than female fertility. The sexual peptide that stimulates the HPG system decreases food intake dimorphism in response to energy availability is at the level of ovulation (Table 1) (reviewed by Donato et al., 2011; Elias and Purohit, 2013; vs. spermatogenesis. Ovulation requires high levels of LH secretion, Hill et al., 2008; Schneider et al., 2012). A notable exception is CRH, whereas spermatogenesis does not. During food restriction, when LH which is released in response to various stressors and is inhibitory for secretion is inhibited, the continued secretion of FSH at high levels food intake, sex behavior, GnRH secretion, and gonadotropin secretion. maintains spermatogenesis for long time periods (Bronson, 1989). The dual action of many of these so-called feeding hormones might J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 719 have been conserved, or might have arisen over and over again hibernation hypophagia has not been documented to the best of our throughout evolution. knowledge. From this line of research important principles have emerged, and In summary, metabolic control of the HPG system and food intake these are applicable to the study of ingestive behavior and the choice are most proximately related to availability of oxidizable metabolic between courtship and foraging. First, the HPG system is primarily fuels. Consistent with this idea, effects of leptin, ghrelin, and possibly responsive to the availability of oxidizable metabolic fuels. The correla- kisspeptin appear to act on the HPG system and food intake via intracel- tions among HPG function, body fat content, and circulating concentra- lular detectors of fuel metabolism such as AMPK and mTOR (Minokoshi tions of leptin are explained by the fact that body fat is a primary source et al., 2008; Roa et al., 2009; Sajapitak et al., 2008 and reviewed by of metabolic fuels, and leptin stimulates fuel oxidation. During food Woods et al., 2008). Estrous cycles, GnRH, and pituitary LH secretion shortages, triglycerides are hydrolyzed and fatty acids are mobilized to are influenced directly by central and peripheral availability of oxidiz- tissues where they can be oxidized. Furthermore, plasma leptin is corre- able fuels, including free fatty acids (Garrel et al., 2011; I'Anson et al., lated with reproductive function, not only because it is correlated with 2003; Sajapitak et al., 2008; Schneider and Wade, 1989; Shahab et al., body fat content, but because leptin stimulates free fatty acid and glu- 2006; Szymanski et al., 2011). cose oxidation (Muoio et al., 1997) and possibly because it inhibits lipogenesis (Buettner et al., 2008). HPG function requires a sufficient supply Summary and conclusions of metabolic fuels, but does not require plasma leptin concentrations to rise above starvation levels. First, in sheep, the pulsatile secretion of LH The chemical messengers listed in Table 1 have profound effects is inhibited by food deprivation and rapidly restored by re-feeding, prior on appetitive aspects of both reproduction and ingestion in addition to increases in body fat content or plasma leptin concentration to their well-known effects on food intake. Mechanisms that control (Szymanski et al., 2007). Second, in hamsters, food deprivation- the choice between food and sex are ancient and they may have been induced anestrous is reversed by re-feeding with no significant in- conserved, since they appear in a wide range of species including creases in plasma leptin concentrations above those of food-deprived invertebrates, amphibians, reptiles, birds, and mammals. Behavioral females (Schneider et al., 2000; Wade et al., 1997). Third, in birds, motivation and the choice between sex and ingestive behavior ap- seasonal fluctuations in reproduction occur independent of leptin pear to be important even in the nematode worm, C. elegans. The ef- (Sharp et al., 2008; Te Marvelde and Visser, 2012). Rather, the HPG sys- fects of hormones on appetitive behaviors are masked when energy tem is controlled by the availability of metabolic fuels, although in is abundant and illuminated when energy is scarce, consistent with some cases, leptin can enhance fuel oxidation. First, in Syrian hamsters, the idea that they function to orchestrate the appetites for food and food deprivation-induced anestrous can be reversed by leptin treat- sex in the face of fluctuations in energy availability. The study of ment, but not when the availability of oxidizable metabolic fuels is both appetitive and consummatory behaviors can be instructive be- blocked using doses of pharmacological inhibitors of glucose and cause appetitive behaviors are often under the control of neural cir- fatty acid oxidation lower than those that induce anestrous in female cuitry and neuropeptide systems that differ from those that control hamsters fed ad libitum (Schneider et al., 1997, 1998). Second, in the performance of ingestion and copulation. The idea that motiva- rats, pulsatile LH secretion is inhibited by fasting or treatment with tion is controlled by an interaction between metabolic fuel availabil- inhibitors of glucose or fatty acid oxidation, but leptin treatments ity and hormones is echoed in examples from species as diverse as that inhibit the secretion of corticosterone fail to restore LH pulses mice, rats, voles, Syrian hamsters, penguins, humming birds, spar- (Nagatani et al., 2001; True et al., 2011). Third, the infertility of the rows, kittiwakes, lizards, garter snakes, and toads. Progress will be ob/ob mutant mouse that lacks a functional leptin protein can be facilitated by location and characterization of the sensory system fully reversed by the addition of a knockout of the CRH gene, and that detects metabolic fuel availability. It will be important this is also true with regard to the hyperphagia and obesity of ob/ob to understand how fuel availability stimulates hormone secretion mice (Wang et al., 2012). and action, as well as how hormones change energy oxidation and These data on leptin and reproduction have parallels to data on storage thereby altering the metabolic stimulus. leptin and food intake. Elevated plasma corticosterone concentrations Ingestive behavior is most often studied in the field, or in laboratory are both necessary and sufficient for the induction of hypothalamic animals housed in isolation in small, confined spaces with few behav- AGRP mRNA with fasting and diabetes (Makimura et al., 2003), two ioral options. Field and laboratory experiments often yield conflicting conditions characterized by hyperphagia. This suggests that leptin results and conclusions. The discrepancies might be resolved by exper- does not inhibit food intake directly, but rather, leptin influences food iments that manipulate metabolic fuel availability and the presence or intake indirectly by its effects on glucocorticoids, hormones with pro- absence of potential mating partners. The key to a realistic and in- found effects on the disposition of metabolic fuels. In a similar vein, depth understanding of the function of neuroendocrine systems might leptin is a poor signal for the decreases in food intake that occur during be attention to a wide range of species studied in a context in which winter hibernation because hibernation requires not only a cessation of critical environmental variables are controlled. Other than the ease of eating but a precipitous drop in metabolic rate and fuel oxidation; lep- genetic manipulation, there is little reason to confine our attention to tin, by contrast, increases metabolic fuel oxidation (Rossetti et al., laboratory rats and mice. 1997). Leptin treatment prevents the onset of daily torpor in both the striped-faced dunnart (Sminthopsis macroura) and the Siberian hamster Acknowledgments (Phodopus sungorus)(Freeman et al., 2004; Geiser et al., 1998). Changes in plasma leptin concentration do not explain seasonal changes in food We extend our heartfelt appreciation to the anonymous reviewers intake in little brown bats (Myotis lucifugus). During prehibernation and the editor who provided critical information, insights, and correc- hyperphagia and body weight gain, plasma leptin concentrations peak tions to the original version of this review. We also thank Jay Alexander well before peaks in body weight and food intake. Thus, high circulating for his outstanding artistic and technical talents exhibited in Figs. 1–5. concentrations of leptin do not prevent prehibernation fattening For astute comments on drafts of the manuscript we thank Amber and hyperphagia and do not explain decreases in food intake during Rice, John Nyby, Murray Itzkowitz, Erica Crespi, Deborah Lutterschmidt, entry into hibernation (Kronfeld-Schor et al., 2000). Thus, though Fran Ebling, and Brian Prendergast. Finally, we thank the Schneider there are correlations between plasma leptin concentrations and body laboratory undergraduates for thorough proof reading and grammar weight over the year in some hibernators (Concannon et al., 2001), advice: Elizabeth Krumm, Ryan Andrews, Brandon Salzman, Joseph this correlation is not present in others (Freeman et al., 2004; Geiser Munier, Connor Funsch, Emma Galarza, Jessica Sevetson, Elise Esposito, et al., 1998), and a causal relationship between plasma leptin and and Emma Newkirk. Nobody does it gooder. 720 J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728

References Beneke, W.M., Davis, C.H., Vander Tuig, J.G., 1988. Effects of a behavioral weight-loss program food purchases: instructions to shop with a list. Int. J. Obes. 12, 335–342. Benoit, S.C., Clegg, D.J., Woods, S.C., Seeley, R.J., 2005. The role of previous exposure in Abizaid, A., 2009. Ghrelin and dopamine: new insights on the peripheral regulation of the appetitive and consummatory effects of orexigenic neuropeptides. Peptides appetite. J. Neuroendocrinol. 21, 787–793. 26, 751–757. Abrahams, M.V., 1993. The trade-off between foraging and courting in male guppies. Bentley, G.E., Jensen, J.P., Kaur, G.J., Wacker, D.W., Tsutsui, K., Wingfield, J.C., 2006. Rapid Anim. Behav. 45, 673–681. inhibition of female sexual behavior by gonadotropin-inhibitory hormone (GnIH). Agmo, A., Picker, Z., 1990. Catecholamines and the initiation of sexual behavior in male Horm. Behav. 49, 550–555. rats without sexual experience. Pharmacol. Biochem. Behav. 35, 327–334. Bernier, N.J., Bedard, N., Peter, R.E., 2004. Effects of cortisol on food intake, growth, and Ahima, R.S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., Flier, J.S., forebrain neuropeptide Y and corticotropin-releasing factor gene expression in gold- 1996. Role of leptin in the neuroendocrine response to fasting. Nature 382, 250–252. fish. Gen. Comp. Endocrinol. 135, 230–240. Alde, S., Celis, M.E., 1980. Influence of alpha-melanotropin on LH release in the rat. Billington, C.J., Morley, J.E., Levine, A.S., Gerritsen, G.C., 1984. Feeding systems in Chinese Neuroendocrinology 31, 116–120. hamsters. Am. J. Physiol. 247, R405–R411. Alderete, M.R., Tokarz, R.R., Crews, D., 1980. Luteinizing hormone-releasing hormone and Blank, J.L., Desjardins, C., 1985. Differential effects of food restriction on pituitary–testicular thyrotropin-releasing hormone induction of female sexual receptivity in the lizard, function in mice. Am. J. Physiol. 248, R181–R189. Anolis carolinensis. Neuroendocrinology 30, 200–205. Blundell, J.E., 1977. Is there a role for serotonin (5-hydroxytryptamine) in feeding? Int. Aleksiuk, M., Gregory, P.T., 1974. Regulation of seasonal mating behavior in Thamnophis J. Obes. 1, 15–42. sirtalis parietalis. Copeia 1974, 681–689. Blundell, J.E., 1986. Serotonin manipulations and the structure of feeding behaviour. Aleksiuk, M., Stewart, K.W., 1971. Seasonal changes in the body composition of the garter Appetite 7, 39–56 (Suppl.). snake (Thamnophis sirtalis parietalis) at northern latitudes [sic]. Ecology 52, 485–490. Boonstra, R., McColl, C., Kavels, T., 2001. Reproduction at all costs: the adaptive stress re- Al-Hourani, H.M., Atoum, M.F., 2007. Body composition, nutrient intake and physical sponse of male arctic ground squirrels. Ecology 82, 1930–1946. activity patterns in young women during Ramadan. Singapore Med. J. 48, Booth, D.A., Brookover, T., 1968. Hunger elicited in the rat by a single injection of bovine 906–910. crystalline insulin. Physiol. Behav. 3, 439–446. Alvarenga, T.A., Andersen, M.L., Velazquez-Moctezuma, J., Tufik, S., 2009. Food restriction Borker, A.S., Mascarenhas, J.F., 1991. Role of acetylcholine and dopamine in dorsal hippo- or sleep deprivation: which exerts a greater influence on the sexual behaviour of campus on hoarding behavior in rats. Indian J. Physiol. Pharmacol. 35, 71–73. male rats? Behav. Brain Res. 202, 266–271. Bradley, A.J., McDonald, I.R., Lee, A.K., 1980. Stress and mortality in a small marsupial Ammar, A.A., Sederholm, F., Saito, T.R., Scheurink, A.J., Johnson, A.E., Sodersten, P., 2000. (Antechinus stuartii, Macleay). Gen. Comp. Endocrinol. 40, 188–200. NPY-leptin: opposing effects on appetitive and consummatory ingestive behavior Briggs, D.I., Andrews, Z.B., 2011. Metabolic status regulates ghrelin function on energy and sexual behavior. Am. J. Physiol. Regul. Integr. Comp. Physiol. 278, R1627–R1633. homeostasis. Neuroendocrinology 93, 48–57. Ammar, A.A., Nergardh, R., Fredholm, B.B., Brodin, U., Sodersten, P., 2005. Intake inhibition Broere, F., Van der Schoot, P., Slob, A.K., 1985. Food conditioning, castration, testosterone by NPY and CCK-8: a challenge of the notion of NPY as an “Orexigen”.Behav.Brain administration and sexual behavior in the male rat. Physiol. Behav. 35, 627–629. Res. 161, 82–87. Bronson, F.H., 1989. Mammalian Reproductive Biology, 1 ed. The University of Chicago Asarian, L., Geary, N., 2006. Modulation of appetite by gonadal steroid hormones. Philos. Press, Chicago and London. Trans. R. Soc. Lond. B Biol. Sci. 361, 1251–1263. Bucholtz, D.C., Chiesa, A., Pappano, W.N., Nagatani, S., Tsukamura, H., Maeda, K.I., Foster, Asarian, L., Geary, N., 2007. Estradiol enhances cholecystokinin-dependent lipid-induced D.L., 2000. Regulation of pulsatile luteinizing hormone secretion by insulin in the satiation and activates estrogen receptor-alpha-expressing cells in the nucleus diabetic male lamb. Biol. Reprod. 62, 1248–1255. tractus solitarius of ovariectomized rats. Endocrinology 148, 5656–5666. Buckley, C.A., Schneider, J.E., 2003. Food hoarding is increased by food deprivation and Astheimer, L.B., Buttemer, W.A., Wingfield, J.C., 1992. Interactions of corticosterone with decreased by leptin treatment in Syrian hamsters. Am. J. Physiol. Regul. Integr. Comp. feeding, activity and metabolism in passerine birds. Ornis Scand. 23, 355–365. Physiol. 285, R1021–R1029. Babu, G.N., Vijayan, E., 1983. Plasma gonadotropin, prolactin levels and hypothalamic Buettner, C., Muse, E.D., Cheng, A., Chen, L., Scherer, T., Pocai, A., Su, K., Cheng, B., Li, X., tyrosine hydroxylase activity following intraventricular bombesin and secretin in Harvey-White, J., Schwartz, G.J., Kunos, G., Rossetti, L., 2008. Leptin controls adipose ovariectomized conscious rats. Brain Res. Bull. 11, 25–29. tissue lipogenesis via central, STAT3-independent mechanisms. Nat. Med. 14, Bailey, C.A., Dela-Fera, M.A., 1995. Central nervous system cholesystokinin and the control 667–675. of feeding. Ann. N. Y. Acad. Sci. 448, 417–423. Buffenstein, R., Poppitt, S.D., McDevitt, R.M., Prentice, A.M., 1995. Food intake and the Baird, J.P., Gray, N.E., Fischer, S.G., 2006. Effects of neuropeptide Y on feeding microstruc- menstrual cycle: a retrospective analysis, with implications for appetite research. ture: dissociation of appetitive and consummatory actions. Behav. Neurosci. 120, Physiol. Behav. 58, 1067–1077. 937–951. Bullivant, S.B., Sellergren, S.A., Stern, K., Spencer, N.A., Jacob, S., Mennella, J.A., McClintock, Baker, J., Fowler, C.W., Antonelis, G.A., 1994. Mass change in fasting immature male northern M.K., 2004. Women's sexual experience during the menstrual cycle: identification of furseals.Can.J.Zool.72,326–329. the sexual phase by noninvasive measurement of luteinizing hormone. J. Sex Res. 41, Ball, G.F., Balthazart, J., 2008. How useful is the appetitive and consummatory distinction 82–93. for our understanding of the neuroendocrine control of sexual behavior? Horm. Buttemer, W.A., Astheimer, L.B., Wingfield, J.C., 1991. The effect of corticosterone on Behav. 53, 307–311. standard metabolic rates of small passerine birds. J. Comp. Physiol. B Biochem. Barash, I.A., Cheung, C.C., Weigle, D.S., Ren, H., Kabigting, E.B., Kuijper, J.L., Clifton, D.K., Syst. Environ. Physiol. 161, 427–431. Steiner, R.A., 1996. Leptin is a metabolic signal to the reproductive system. Endocri- Cabanac, M., Richard, D., 1995. Acute intraventricular CRF lowers the hoarding threshold nology 137, 3144–3147. in male rats. Physiol. Behav. 57, 705–710. Barrett, P., Ebling, F.J., Schuhler, S., Wilson, D., Ross, A.W., Warner, A., Jethwa, P., Boelen, A., Cabanac, M., Dagnault, A., Richard, D., 1997. The food-hoarding threshold is not raised by Visser, T.J., Ozanne, D.M., Archer, Z.A., Mercer, J.G., Morgan, P.J., 2007. Hypothalamic acute intraventricular NPY in male rats. Physiol. Behav. 61, 131–135. thyroid hormone catabolism acts as a gatekeeper for the seasonal control of body Campfield, L.A., Smith, F.J., Guisez, Y., Devos, R., Burn, P., 1995. Recombinant mouse weight and reproduction. Endocrinology 148, 3608–3617. ob protein: evidence for a peripheral signal linking adiposity and central neural Barsh, G.S., Schwartz, M.W., 2002. Genetic approaches to studying energy balance: per- networks. Science 269, 546–549. ception and integration. Nat. Rev. Genet. 3. Cansell, C., Denis, R.G., Joly-Amado, A., Castel, J., Luquet, S., 2012. Arcuate AgRP neurons Bartness, T.J., 1997. Food hoarding is increased by pregnancy, lactation, and food depriva- and the regulation of energy balance. Front. Endocrinol. 3, 169. tion in Siberian hamsters. Am. J. Physiol. 272, R118–R125. Caro, J.F., Kolaczynski, J.W., Nyce, M.R., Ohannesian, J.P., Opentanova, I., Goldman, W.H., Bartness, T.J., Clein, M.R., 1994. Effects of food deprivation and restriction, and metabolic Lynn, R.B., Zhang, P.L., Sinha, M.K., Considine, R.V., 1996. Decreased cerebrospinal- blockers on food hoarding in Siberian hamsters. Am. J. Physiol. 266, R1111–R1117. fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet Bartness, T.J., Morley, J.E., Levine, A.S., 1995. Effects of food deprivation and metabolic fuel 348, 159–161. utilization on the photoperiodic control of food intake in Siberian hamsters. Physiol. Carpenter, A.M., Carr, J.A., 1996. The effects of melanocortin peptides and corticosterone Behav. 57, 61–68. on habituation in the great plains toad, Bufo cognatus. Horm. Behav. 30, 236–243. Bartness, T.J., Keen-Rhinehart, E., Dailey, M.J., Teubner, B.J., 2011. Neural and hormonal Carr, J.A., 2002. Stress, neuropeptides, and feeding behavior: a comparative perspective. control of food hoarding. Am. J. Physiol. Regul. Integr. Comp. Physiol. 301, R641–R655. Integr. Comp. Biol. 42, 582–590. Bassi, M., do Carmo, J.M., Hall, J.E., da Silva, A.A., 2012. Chronic effects of centrally admin- Carragher, J.F., Sumpter, J.P., Pottinger, T.G., Pickering, A.D., 1989. The deleterious effects of istered adiponectin on appetite, metabolism and blood pressure regulation in normo- cortisol implantation on reproductive function in two species of trout, Salmo trutta L. tensive and hypertensive rats. Peptides 37, 1–5. and Salmo gairdneri Richardson. Gen. Comp. Endocrinol. 76, 310–321. Basso, A.M., Kelley, A.E., 1999. Feeding induced by GABA(A) receptor stimulation within Cease, A.J., Lutterschmidt, D.I., Mason, R.T., 2007. Corticosterone and the transition from the nucleus accumbens shell: regional mapping and characterization of macronutri- courtship behavior to dispersal in male red-sided garter snakes (Thamnophis sirtalis ent and taste preference. Behav. Neurosci. 113, 324–336. parietalis). Gen. Comp. Endocrinol. 150, 124–131. Beak, S.A., Heath, M.M., Small, C.J., Morgan, D.G., Ghatei, M.A., Taylor, A.D., Buckingham, Chakraborty, M., Burmeister, S.S., 2009. Estradiol induces sexual behavior in female J.C., Bloom, S.R., Smith, D.M., 1998. Glucagon-like peptide-1 stimulates luteinizing tungara frogs. Horm. Behav. 55, 106–112. hormone-releasing hormone secretion in a rodent hypothalamic neuronal cell line. Chappell, P.E., Levine, J.E., 2000. Stimulation of gonadotropin-releasing hormone surges J. Clin. Invest. 101, 1334–1341. by estrogen. I. Role of hypothalamic progesterone receptors. Endocrinology 141, Beaujean, D., Do-Rego, J.L., Galas, L., Mensah-Nyagan, A.G., Fredriksson, R., Larhammar, D., 1477–1485. Fournier, A., Luu-The, V., Pelletier, G., Vaudry, H., 2002. Neuropeptide Y inhibits the Chavez, M., Kaiyala, K., Madden, L.J., Schwartz, M.W., Woods, S.C., 1995. Intraventricular in- biosynthesis of sulfated neurosteroids in the hypothalamus through activation of sulin and the level of maintained body weight in rats. Behav. Neurosci. 109, 528–531. Y(1) receptors. Endocrinology 143, 1950–1963. Chazal, G., Faudon, M., Gogan, F., Laplante, E., 1974. Negative and positive effects of Beneke, W.M., Davis, C.H., 1985. Relationship of hunger, use of a shopping list and obesity oestradiol upon luteinizing hormone secretion in the female rat. J. Endocrinol. 61, to food purchases. Int. J. Obes. 9, 391–399. 511–512. J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 721

Cheng, M., 1973. Effect of estrogen on behavior of ovariectomized ring doves (Streptopelia Dailey, M.E., Bartness, T.J., 2008. Fat pad-specific effects of lipectomy on foraging, food risoria). J. Comp. Physiol. Psychol. 83, 234–239. hoarding, and food intake. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, Cheng, C.Y., Chu, J.Y., Chow, B.K., 2011a. Central and peripheral administration of secretin R321–R328. inhibits food intake in mice through the activation of the melanocortin system. Dailey, M.J., Bartness, T.J., 2009. Appetitive and consummatory ingestive behaviors stimu- Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol. 36, 459–471. lated by PVH and perifornical area NPY injections. Am. J. Physiol. Regul. Integr. Comp. Cheng, X.B., Wen, J.P., Yang, J., Yang, Y., Ning, G., Li, X.Y., 2011b. GnRH secretion is Physiol. 296, R877–R892. inhibited by adiponectin through activation of AMP-activated protein kinase and Dailey, M.J., Bartness, T.J., 2010. Arcuate nucleus destruction does not block food deprivation- extracellular signal-regulated kinase. Endocrine 39, 6–12. induced increases in food foraging and hoarding. Brain Res. 1323, 94–108. Cherel, Y., Robin, J.P., Walch, O., Karmann, H., Netchitailo, P., Le Maho, Y., 1988. Fasting in Daniel, J.A., Thomas, M.G., Hale, C.S., Simmons, J.M., Keisler, D.H., 2000. Effect of king penguin. I. Hormonal and metabolic changes during breeding. Am. J. Physiol. cerebroventricular infusion of insulin and (or) glucose on hypothalamic expression 254, R170–R177. of leptin receptor and pituitary secretion of LH in diet-restricted ewes. Domest. Chianese, R., Ciaramella, V., Fasano, S., Pierantoni, R., Meccariello, R., 2013. Kisspeptin Anim. Endocrinol. 18, 177–185. receptor, GPR54, as a candidate for the regulation of testicular activity in the frog Dark, J., 2005. Annual lipid cycles in hibernators: integration of physiology and behavior. Rana esculenta. Biol. Reprod. 88, 73. Annu. Rev. Nutr. 25, 469–497. Chowdhury, V.S., Yoshimura, Y., 2004. Changes in the responsiveness of hen anterior Darwin, C., 1859. The Origin of Species. Penguin Group, London. pituitary to cLHRH-II during induced molting. Domest. Anim. Endocrinol. 26, 351–359. Davidson, J.M., 1966. Activation of the male rat's sexual behavior by intracerebral implan- Ciaccio, L.A., Lisk, R.D., 1973. Central control of estrous behavior in the female golden tation of androgens. Endocrinology 79, 783–794. hamster. Estrogen sensitivity within the hypothalamus. Neuroendocrinology 13, Davidson, J.M., Bloch, G.J., 1969. Neuroendocrine aspects of male reproduction. Biol. 21–28. Reprod. 1 (Suppl. 1), 67–92. Ciaccio, L.A., Lisk, R.D., Reuter, L.A., 1979. Prelordotic behavior in the hamster: a hormon- Day, D.E., Bartness, T.J., 2004. Agouti-related protein increases food hoarding more than ally modulated transition from aggression to sexual receptivity. J. Comp. Physiol. food intake in Siberian hamsters. Am. J. Physiol. Regul. Integr. Comp. Physiol. 286, Psychol. 93, 771–780. R38–R45. Clarke, I.J., Cummins, J.T., 1982. The temporal relationship between gonadotropin releasing Day, D.E., Mintz, E.M., Bartness, T.J., 1999. Diet self-selection and food hoarding after food hormone (GnRH) and luteinizing hormone (LH) secretion in ovariectomized ewes. deprivation by Siberian hamsters. Physiol. Behav. 68, 187–194. Endocrinology 111, 1737–1739. Day, D.E., Keen-Rhinehart, E., Bartness, T.J., 2005. Role of NPY and its receptor subtypes in Clarke, I.J., Horton, R.J., Doughton, B.W., 1990. Investigation of the mechanism by which foraging, food hoarding, and food intake by Siberian hamsters. Am. J. Physiol. Regul. insulin-induced hypoglycemia decreases luteinizing hormone secretion in ovariecto- Integr. Comp. Physiol. 289, R29–R36. mized ewes. Endocrinology 127, 1470–1476. de Jonge, F.H., Kalverdijk, E.H., van de Poll, N.E., 1986. Androgens are specifically implicated Clarke, I.J., Smith, J.T., Henry, B.A., Oldfield, B.J., Stefanidis, A., Millar, R.P., Sari, I.P., Chng, K., in female rat sexual motivation. The influence of methyltrienelone (R1881) on sexual Fabre-Nys, C., Caraty, A., Ang, B.T., Chan, L., Fraley, G.S., 2012. Gonadotropin-inhibitory orientation. Pharmacol. Biochem. Behav. 24, 285–289. hormone is a hypothalamic peptide that provides a molecular switch between repro- De Pedro, N., Alonso-Gomez, A.L., Gancedo, B., Delgado, M.J., Alonso-Bedate, M., 1993. Role duction and feeding. Neuroendocrinology 95, 305–315. of corticotropin-releasing factor (CRF) as a food intake regulator in goldfish. Physiol. Clegg, D.J., Brown, L.M., Zigman, J.M., Kemp, C.J., Strader, A.D., Benoit, S.C., Woods, S.C., Behav. 53, 517–520. Mangiaracina, M., Geary, N., 2007. Estradiol-dependent decrease in the orexigenic De Pedro, N., Cespedes, M.V., Delgado, M.J., Alonso-Bedate, M., 1995a. The galanin- potency of ghrelin in female rats. Diabetes 56, 1051–1058. induced feeding stimulation is mediated via alpha 2-adrenergic receptors in goldfish. Coen, C.W., MacKinnon, P.C., 1979. Serotonin involvement in the control of phasic Regul. Pept. 57, 77–84. luteinizing hormone release in the rat: evidence for a critical period. J. Endocrinol. de Pedro, N., Delgado, M.J., Alonso-Bedate, M., 1995b. Central administration of beta- 82, 105–113. endorphin increases food intake in goldfish: pretreatment with the opioid antagonist Coen, C.W., Franklin, M., Laynes, R.W., MacKinnon, P.C., 1980. Effects of manipulating naloxone. Regul. Pept. 55, 189–195. serotonin on the incidence of ovulation in the rat. J. Endocrinol. 87, 195–201. de Pedro, N., Lopez-Patino, M.A., Guijarro, A.I., Pinillos, M.L., Delgado, M.J., Alonso-Bedate, Concannon, P., Levac, K., Rawson, R., Tennant, B., Bensadoun, A., 2001. Seasonal changes in M., 2000. NPY receptors and opioidergic system are involved in NPY-induced feeding serum leptin, food intake, and body weight in photoentrained woodchucks. Am. in goldfish. Peptides 21, 1495–1502. J. Physiol. Regul. Integr. Comp. Physiol. 281, R951–R959. DeFazio, R.A., Heger, S., Ojeda, S.R., Moenter, S.M., 2002. Activation of A-type gamma- Cooke, S.J., Philipp, D.P., Wahl, D.H., Weatherhead, P.J., 2006. Energetics of parental care in aminobutyric acid receptors excites gonadotropin-releasing hormone neurons. Mol. six syntopic centrarchid fishes. Oecologia 148, 235–249. Endocrinol. 16, 2872–2891. Coppari, R., Ichinose, M., Lee, C.E., Pullen, A.E., Kenny, C.D., McGovern, R.A., Tang, V., Liu, Dempsey, E.W., Hertz, R., Young, W.C., 1936. The experimental induction of oestrus S.M., Ludwig, T., Chua Jr., S.C., Lowell, B.B., Elmquist, J.K., 2005. The hypothalamic (sexual receptivity) in the normal and ovariectomized guinea pig. Am. J. Physiol. arcuate nucleus: a key site for mediating leptin's effects on glucose homeostasis 116, 201–209. and locomotor activity. Cell Metab. 1, 63–72. Denbow, D.M., 1983. Food intake and temperature response to injections of catechol- Cornil, C.A., Dejace, C., Ball, G.F., Balthazart, J., 2005. Dopamine modulates male sexual amines into the lateral ventricle of the turkey brain. Poult. Sci. 62, 1088–1092. behavior in Japanese quail in part via actions on noradrenergic receptors. Behav. Denbow, D.M., Van Krey, H.P., Cherry, J.A., 1982. Feeding and drinking response of young Brain Res. 163, 42–57. chicks to injections of serotonin into the lateral ventricle of the brain. Poult. Sci. 61, Cote, J., Clobert, J., Montes Poloni, L., Haussy, C., Meylan, S., 2010. Food deprivation 150–155. modifies corticosterone-dependent behavioural shifts in the common lizard. Gen. Denbow, D.M., Snapir, N., Furuse, M., 1999. Inhibition of food intake by CRF in chickens. Comp. Endocrinol. 166, 142–151. Physiol. Behav. 66, 645–649. Cox, N.M., Stuart, M.J., Althen, T.G., Bennett, W.A., Miller, H.W., 1987. Enhancement of Deviche, P., Schepers, G., 1984. Intracerebroventricular injection of ostrich beta- ovulation rate in gilts by increasing dietary energy and administering insulin during endorphin to satiated pigeons induces hyperphagia but not hyperdipsia. Peptides 5, follicular growth. J. Anim. Sci. 64, 507–516. 691–694. Craig, W., 1917. Appetites and aversions as constituents of instinct. Proc. Natl. Acad. Sci. 3, Dewasmes, G., Le Maho, Y., Cornet, A., Groscolas, R., 1980. Resting metabolic rate and cost 685–688. of locomotion in long-term fasting emperor penguins. J. Appl. Physiol. 49, 888–896. Crespi, E.J., Denver, R.J., 2006. Leptin (ob gene) of the South African clawed frog Xenopus Dewsbury, D.A., 1982. Ejaculate cost and mate choice. Am. Nat. 119, 601–610. laevis. Proc. Natl. Acad. Sci. U.S.A. 103, 10092–10097. Dhillon, H., Zigman, J.M., Ye, C., Lee, C.E., McGovern, R.A., Tang, V., Kenny, C.D., Crespi, E.J., Vaudry, H., Denver, R.J., 2004. Roles of corticotropin-releasing factor, neuro- Christiansen, L.M., White, R.D., Edelstein, E.A., Coppari, R., Balthasar, N., Cowley, peptide Y and corticosterone in the regulation of food intake in Xenopus laevis. M.A., Chua Jr., S., Elmquist, J.K., Lowell, B.B., 2006. Leptin directly activates SF1 J. Neuroendocrinol. 16, 279–288. neurons in the VMH, and this action by leptin is required for normal body-weight Crews, D., 1975. Psychobiology of reptilian reproduction. Science 189, 1059–1065. homeostasis. Neuron 49, 191–203. Crews, D., Grassman, M., Halpert, A., Camazine, B., 1987. Sex and seasonal differences in DiBattista, D., Sitzer, C.A., 1994. Dietary variety enhances meal size in golden hamsters. metabolism in the red-sided garter snake, Thamnophis sirtalis parietalis.Can.J.Zool. Physiol. Behav. 55, 381–383. 65, 2362–2368. Dodd, D.K., Stalling, R.B., Bedell, J., 1977. Grocery purchases as a function of obesity and Crowley, W.R., Tessel, R.E., O'Donohue, T.L., Adler, B.A., Kalra, S.P., 1985. Effects of ovarian assumed food deprivation. Int. J. Obes. 1, 43–47. hormones on the concentrations of immunoreactive neuropeptide Y in discrete brain Donato Jr., J., Cravo, R.M., Frazao, R., Elias, C.F., 2011. Hypothalamic sites of leptin action regions of the female rat: correlation with serum luteinizing hormone (LH) and linking metabolism and reproduction. Neuroendocrinology 93, 9–18. median eminence LH-releasing hormone. Endocrinology 117, 1151–1155. Dooley, J.C., Prendergast, B.J., 2012. Photorefractoriness and energy availability interact to Crowley, M.A., Smart, J.L., Rubinstein, M., Cerdans, M.G., Diano, S., Horvath, T.L., Cone, R.D., permit facultative timing of spring breeding. Behav. Ecol. 23, 1049–1058. Low, M.J., 2001. Leptin activates anorexigenic POMC neurons through a neural Dornan, W.A., Bloch, G.J., Priest, C.A., Micevych, P.E., 1989. Microinjection of cholecystoki- network in the arcuate nucleus. Nature 411, 480–484. nin into the medial preoptic nucleus facilitates lordosis behavior in the female rat. Crown, A., Clifton, D.K., Steiner, R.A., 2007. Neuropeptide signaling in the integration of Physiol. Behav. 45, 969–974. metabolism and reproduction. Neuroendocrinology 86, 175–182. Drewett, R.F., 1973. Sexual behaviour and sexual motivation in the female rat. Nature 242, Cusin, I., Rohner-Jeanrenaud, F., Stricker-Krongrad, A., Jeanrenaud, B., 1996. The weight- 476–477. reducing effect of an intracerebroventricular bolus injection of leptin in genetically Durante, K.M., Li, N.P., 2009. Oestradiol level and opportunistic mating in women. Biol. obese fa/fa rats. Reduced sensitivity compared with lean animals. Diabetes 45, Lett. 5, 179–182. 1446–1450. Ebling, F.J., Arthurs, O.J., Turney, B.W., Cronin, A.S., 1998. Seasonal neuroendocrine rhythms da Silva, E.S., dos Santos, T.V., Hoeller, A.A., dos Santos, T.S., Pereira, G.V., Meneghelli, C., in the male Siberian hamster persist after monosodium glutamate-induced lesions of Pezlin, A.I., dos Santos, M.M., Faria, M.S., Paschoalini, M.A., Marino-Neto, J., 2008. the arcuate nucleus in the neonatal period. J. Neuroendocrinol. 10, 701–712. Behavioral and metabolic effects of central injections of orexins/hypocretins in Eckel, L.A., 2011. The ovarian hormone estradiol plays a crucial role in the control of food pigeons (Columba livia). Regul. Pept. 147, 1–3. intake in females. Physiol. Behav. 104, 517–524. 722 J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728

Elias, C.F., Purohit, D., 2013. Leptin signaling and circuits in puberty and fertility. Cell. Mol. Ganesh, C.B., Chabbi, A., 2013. Naltrexone attenuates stress-induced suppression of LH Life Sci. 70, 841–862. secretion in the pituitary gland in the Cichlid fish Oreochromis mossambicus:evidence Etches, R.J., Cunningham, F.J., 1976. The effect of pregnenolone, progesterone, deoxycor- for the opioidergic mediation of reproductive stress response. Fish Physiol. Biochem. ticosterone or corticosterone on the time of ovulation and oviposition in the hen. Br. 39, 627–636. Poultry Sci. 17, 637–642. Gangestad, S.W., 2001. Adaptive design, selective history, and women's sexual motiva- Etches, R.J., Williams, J.B., Rzasa, J., 1984. Effects of corticosterone and dietary changes in tions. Nebr. Symp. Motiv. 47, 37–74. the hen on ovarian function, plasma LH and steroids and the response to exogenous Gangestad, S.W., Thornhill, R., 2008. Human oestrus. Proc. Biol. Sci. 275, 991–1000. LH–RH. J. Reprod. Fertil. 70, 121–130. Gao, Q., Mezei, G., Nie, Y., Rao, Y., Choi, C.S., Bechmann, I., Leranth, C., Toran-Allerand, D., Etgen, A.M., Acosta-Martinez, M., 2003. Participation of growth factor signal transduction Priest, C.A., Roberts, J.L., Gao, X.B., Mobbs, C., Shulman, G.I., Diano, S., Horvath, T.L., pathways in estradiol facilitation of female reproductive behavior. Endocrinology 2007. Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin 144, 3828–3835. cells and Stat3 signaling in obese animals. Nat. Med. 13, 89–94. Everitt, B.J., 1990. Sexual motivation: a neural and behavioural analysis of the mecha- Garrel, G., Simon, V., Denoyelle, C., Cruciani-Guglielmacci, C., Migrenne, S., Counis, R., nisms underlying appetitive and copulatory responses of male rats. Neurosci. Magnan, C., Cohen-Tannoudji, J., 2011. Unsaturated fatty acids stimulate LH secretion Biobehav. Rev. 14, 217–232. via novel PKCepsilon and -theta in gonadotrope cells and inhibit GnRH-induced LH Everitt, B.J., Herbert, J., 1970. The maintenance of sexual receptivity by adrenal androgens release. Endocrinology 152, 3905–3916. in female rhesus monkeys. J. Endocrinol. 48, 38. Garthwaite, T.L., 1985. Peripheral motilin administration stimulates feeding in fasted rats. Ewert, J.P., Buxbaum-Conradi, H., Glagow, M., Rottgen, A., Schurg-Pfeiffer, E., Schwippert, Peptides 6, 41–44. W.W., 1999. Forebrain and midbrain structures involved in prey-catching behaviour Gattermann, R., Johnston, R.E., Yigit, N., Fritzsche, P., Larimer, S., Ozkurt, S., Neumann, K., of toads: stimulus-response mediating circuits and their modulating loops. Eur. Song, Z., Colak, E., Johnston, J., McPhee, M.E., 2008. Golden hamsters are nocturnal J. Morphol. 37, 172–176. in captivity but diurnal in nature. Biol. Lett. 4, 253–255. Ewert, J.P., Buxbaum-Conradi, H., Dreisvogt, F., Glagow, M., Merkel-Harff, C., Rottgen, A., Gavassa, S., Stoddard, P.K., 2012. Food restriction promotes signaling effort in response to Schurg-Pfeiffer, E., Schwippert, W.W., 2001. Neural modulation of visuomotor func- social challenge in a short-lived electric fish. Horm. Behav. 62, 381–388. tions underlying prey-catching behaviour in anurans: perception, attention, motor Gavaud, J., 1986. Vitellogenesis in the lizard Lacerta vivipara jacquin.II.Vitellogeninsyn- performance, learning. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 128, 417–461. thesis during the reproductive cycle and its control by ovarian steroids. Gen. Comp. Facciolo, R.M., Crudo, M., Zizza, M., Giusi, G., Canonaco, M., 2011. Feeding behaviors and Endocrinol. 63, 11–23. ORXR-beta-GABA A R subunit interactions in Carassius auratus. Neurotoxicol. Teratol. Geary, N., Asarian, L., Korach, K.S., Pfaff, D.W., Ogawa, S., 2001. Deficits in E2-dependent 33, 641–650. control of feeding, weight gain, and cholecystokinin satiation in ER-alpha null mice. Fantino, M., Cabanac, M., 1984. Effect of a cold ambient temperature on the rat's food Endocrinology 142, 4751–4757. hoarding behavior. Physiol. Behav. 32, 183–190. Geiser, F., Kortner, G., Schmidt, I., 1998. Leptin increases energy expenditure of a marsu- Faulconbridge, L.F., Grill, H.J., Kaplan, J.M., 2005. Distinct forebrain and caudal brainstem pial by inhibition of daily torpor. Am. J. Physiol. 275, R1627–R1632. contributions to the neuropeptide Y mediation of ghrelin hyperphagia. Diabetes 54, Gibbins, A.M., Robinson, G.A., 1982a. Comparative study of the physiology of vitel- 1985–1993. logenesisinJapanesequail.Comp.Biochem.Physiol.AComp.Physiol.72, Fernald, R.D., Hirata, N.R., 1977. Field study of Haplochromis burtoni: quantitative behav- 149–155. ioural observations. Anim. Behav. 25, 964–975. Gibbins, A.M., Robinson, G.A., 1982b. A comparison of diethylstilbestrol- and estradiol-17 Fernandez-Fernandez, R., Tena-Sempere, M., Aguilar, E., Pinilla, L., 2004. Ghrelin effects on beta-induced vitellogenesis in quail. Poult. Sci. 61, 1188–1193. gonadotropin secretion in male and female rats. Neurosci. Lett. 362, 103–107. Gibbs, J., Young, R.C., Smith, G.P., 1973. Cholecystokinin decreases food intake in rats. Fernandez-Fernandez, R., Martini, A.C., Navarro, V.M., Castellano, J.M., Dieguez, C., Aguilar, J. Comp. Physiol. Psychol. 84, 488–495. E., Pinilla, L., Tena-Sempere, M., 2006. Novel signals for the integration of energy Gibbs, J., Fauser, D.J., Rowe, E.A., Rolls, B.J., Rolls, E.T., Maddison, S.P., 1979. Bombesin balance and reproduction. Mol. Cell. Endocrinol. 254–255, 127–132. suppresses feeding in rats. Nature 282, 208–210. Fessler, D.M.T., 2003. No time to eat: an adaptationist account of periovulatory behavioral Girish, S., Saidapur, S.K., 2000. Interrelationship between food availability, fat body, and changes. Q. Rev. Biol. 78, 3–21. ovarian cycles in the frog, Rana tigrina, with a discussion on the role of fat body in Figlewicz, D.P., Sipols, A.J., Porte Jr., D., Woods, S.C., Liddle, R.A., 1989. Intraventricular CCK anuran reproduction. J. Exp. Zool. 286, 487–493. inhibits food intake and gastric emptying in baboons. Am. J. Physiol. 256, R1313–R1317. Gittleman, J.L., Thompson, S.D., 1988. Energy allocation in mammalian reproduction. Am. Florant, G.L., Healy, J.E., 2012. The regulation of food intake in mammalian hibernators: a Zool. 28, 863–875. review. J. Comp. Physiol. B Biochem. Syst. Environ. Physiol. 182, 451–467. Glagow, M., Ewert, J.P., 1994. Increases of excitatory receptive fields of retinal ganglion Foltin, R.W., 2005. Effects of dietary and pharmacological manipulations on appetitive and cells in common toads under apomorphine are not associated with size preference consummatory aspects of feeding in non-human primates. Appetite 45, 110–120. in prey-snapping. Neurosci. Lett. 173, 83–86. Freeman, D.A., Lewis, D.A., Kauffman, A.S., Blum, R.M., Dark, J., 2004. Reduced leptin con- Glagow, M., Ewert, J.P., 1996. Apomorphine-induced suppression of prey oriented turning centrations are permissive for display of torpor in Siberian hamsters. Am. J. Physiol. in toads is correlated with activity changes in pretectum and tectum: [14C]2DG Regul. Integr. Comp. Physiol. 287, R97–R103. studies and single cell recordings. Neurosci. Lett. 220, 215–218. Friedman, M.I., 1977. Insulin-induced hyperphagia in alloxan-diabetic rats fed a high-fat Glagow, M., Ewert, J.P., 1997a. Dopaminergic modulation of visual responses in toads. I. diet. Physiol. Behav. 19, 597–599. Apomorphine-induced effects on visually directed appetitive and consummatory Friedman, M.I., 1989. Metabolic control of food intake. Bol. Asoc. Med. P. R. 81, 111–113. prey-catching behavior. J. Comp. Physiol. A 180, 1–9. Friedman, M.I., 1992. Integrated metabolic control of food intake. Appetite 18, 243. Glagow, M., Ewert, J.P., 1997b. Dopaminergic modulation of visual responses in toads. II. Friedman, M.I., 1998. Fuel partitioning and food intake. Am. J. Clin. Nutr. 67, 513S–518S. Influences of apomorphine on retinal ganglion cells and tectal cells. J. Comp. Physiol. Friedman, M.I., 2008. Food intake: control, regulation and the illusion of dysregulation. In: A 180, 11–18. Harris, R.B., Mattes, R. (Eds.), Appetite and Food Intake: Behavioral and Physiological Glagow, M., Ewert, J., 1999. Apomorphine alters prey-catching patterns in the common Considerations. CRC Press, Boca Raton, Florida, USA, pp. 1–19. toad: behavioral experiments and (14)C-2-deoxyglucose brain mapping studies. Friedman, M.I., Ramirez, I., Wade, G.N., Siegel, L.I., Granneman, J., 1982. Metabolic and phys- Brain Behav. Evol. 54, 223–242. iologic effects of a hunger-inducing injection of insulin. Physiol. Behav. 29, 515–518. Goldstein, R.J., 1973. Cichlids of the World. T. F. H. Publications, Inc., Neptune City, N.J. Friedman, M.I., Tordoff, M.G., Ramirez, I., 1986. Integrated metabolic control of food Gosselin, C., Cabanac, M., 1997. Adrenalectomy lowers the body weight set-point in rats. intake. Brain Res. Bull. 17, 855–859. Physiol. Behav. 62, 519–523. Friedman, M.I., Harris, R.B., Ji, H., Ramirez, I., Tordoff, M.G., 1999. Fatty acid oxidation af- Gottsch, M.L., Cunningham, M.J., Smith, J.T., Popa, S.M., Acohido, B.V., Crowley, W.F., fects food intake by altering hepatic energy status. Am. J. Physiol. 276, R1046–R1053. Seminara, S., Clifton, D.K., Steiner, R.A., 2004. A role for kisspeptins in the regulation Friedman, M.I., Graczyk-Millbrandt, G., Ji, H., Rawson, N.E., Osbakken, M.D., 2003. 2,5- of gonadotropin secretion in the mouse. Endocrinology 145, 4073–4077. Anhydro-D-mannitol increases hepatocyte sodium: transduction of a hepatic hunger Govic, A., Levay, E.A., Hazi, A., Penman, J., Kent, S., Paolini, A.G., 2008. Alterations in male stimulus? Biochim. Biophys. Acta 1642, 53–58. sexual behaviour, attractiveness and testosterone levels induced by an adult-onset Fruebis, J., Tsao, T.S., Javorschi, S., Ebbets-Reed, D., Erickson, M.R., Yen, F.T., Bihain, B.E., calorie restriction regimen. Behav. Brain Res. 190, 140–146. Lodish, H.F., 2001. Proteolytic cleavage product of 30-kDa adipocyte complement- Grandison, L., Guidotti, A., 1977. Stimulation of food intake by muscimol and beta endor- related protein increases fatty acid oxidation in muscle and causes weight loss in phin. Neuropharmacology 16, 533–536. mice. Proc. Natl. Acad. Sci. U.S.A. 98, 2005–2010. Gray, J.M., Wade, G.N., 1981. Food intake, body weight, and adiposity in female rats: Fujihara, N., Shiino, M., 1983. Stimulatory effect of thyrotrophin-releasing hormone (TRH) actions and interactions of progestins and antiestrogens. Am. J. Physiol. 240, on the release of luteinizing hormone (LH) from rat anterior pituitary cells in vitro. E474–E481. Can. J. Physiol. Pharmacol. 61, 186–189. Gregory, P.T., 1977. Life-history parameters of the red-sided garter snake (Thamnophis Furuse, M., Matsumoto, M., Saito, N., Sugahara, K., Hasegawa, S., 1997. The central sirtalis parietalis) in an extreme environment, the Interlake region of Manitoba. Nat. corticotropin-releasing factor and glucagon-like peptide-1 in food intake of the neo- Mus. Can. Pub. Zool. 13, 1–44. natal chick. Eur. J. Pharmacol. 339, 211–214. Grey, C.L., Grayfer, L., Belosevic, M., Chang, J.P., 2010. Ghrelin stimulation of gonadotropin Furuta, M., Funabashi, T., Kimura, F., 2001. Intracerebroventricular administration of (LH) release from goldfish pituitary cells: presence of the growth hormone secreta- ghrelin rapidly suppresses pulsatile luteinizing hormone secretion in ovariectomized gogue receptor (GHS-R1a) and involvement of voltage-sensitive Ca2+ channels. rats. Biochem. Biophys. Res. Commun. 288, 780–785. Mol. Cell. Endocrinol. 317, 64–77. Furuta, M., Funabashi, T., Kimura, F., 2002. Suppressive action of orexin A on pulsatile Griffiths, S.W., 1996. Sex differences in the trade-off between feeding and mating in the luteinizing hormone secretion is potentiated by a low dose of estrogen in ovariecto- guppy. Fish Biol. 48, 891–898. mized rats. Neuroendocrinology 75, 151–157. Grill, H.J., 2006. Distributed neural control of energy balance: contributions from hind- Furuta, M., Mitsushima, D., Shinohara, K., Kimura, F., Funabashi, T., 2010. Food availability brain and hypothalamus. Obesity (Silver Spring) 14 (Suppl. 5), 216S–221S. affects orexin a/hypocretin-1-induced inhibition of pulsatile luteinizing hormone Grill, H.J., 2010. Leptin and the systems neuroscience of meal size control. Front. secretion in female rats. Neuroendocrinology 91, 41–47. Neuroendocrinol. 31, 61–78. J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 723

Grill, H.J., Hayes, M.R., 2009. The nucleus tractus solitarius: a portal for visceral afferent Holland, K.L., Popper, P., Micevych, P.E., 1997. Infusion of CCK-A receptor mRNA antisense signal processing, energy status assessment and integration of their combined effects oligodeoxynucleotides inhibits lordosis behavior. Physiol. Behav. 62, 537–543. on food intake. Int. J. Obes. (Lond) 33 (Suppl. 1), S11–S15. Holmberg, B.J., Morrison, C.D., Keisler, D.H., 2001. Endocrine responses of ovariectomized Grill, H.J., Kaplan, J.M., 1990. Caudal brainstem participates in the distributed neural ewes to i.c.v. infusion of urocortin. J. Endocrinol. 171, 517–524. control of feeding. In: Stricker, E.M. (Ed.), Handbook of Behavioral Neurobiology: Horn, C.C., Ji, H., Friedman, M.I., 2004. Etomoxir, a fatty acid oxidation inhibitor, increases Neurobiology of Food and Fluid Intake. Plenum Press, New York, pp. 125–150. food intake and reduces hepatic energy status in rats. Physiol. Behav. 81, 157–162. Grill, H.J., Kaplan, J.M., 1992. Sham feeding in intact and chronic decerebrate rats. Am. Hoskins, L.J., Xu, M., Volkoff, H., 2008. Interactions between gonadotropin-releasing hor- J. Physiol. 262, R1070–R1074. mone (GnRH) and orexin in the regulation of feeding and reproduction in goldfish Grill, H.J., Kaplan, J.M., 2001. Interoceptive and integrative contributions of forebrain and (Carassius auratus). Horm. Behav. 54, 379–385. brainstem to energy balance control. Int. J. Obes. Relat. Metab. Disord. 25 (Suppl. 5), Houpt, T.R., 1974. Stimulation of food intake in ruminants by 2-deoxy-D-glucose and S73–S77. insulin. Am. J. Physiol. 227, 161–167. Grill, H.J., Kaplan, J.M., 2002. The neuroanatomical axis for control of energy balance. Howland, B.E., 1975. The influence of feed restriction and subsequent re-feeding on Front. Neuroendocrinol. 23, 2–40. gonadotrophin secretion and serum testosterone levels in male rats. J. Reprod. Fertil. Grill, H.J., Norgren, R., 1978. The taste reactivity test. I. Mimetic responses to gustatory 44, 429–436. stimuli in neurologically normal rats. Brain Res. 143, 263–279. Hughes, A.M., Everitt, B.J., Herbert, J., 1987. Selective effects of beta-endorphin infused Grill, H.J., Ginsberg, A.B., Seeley, R.J., Kaplan, J.M., 1998. Brainstem application of into the hypothalamus, preoptic area and bed nucleus of the stria terminalis on the melanocortin receptor ligands produces long-lasting effects on feeding and body sexual and ingestive behaviour of male rats. Neuroscience 23, 1063–1073. weight. J. Neurosci. 18, 10128–10135. Hughes, A.M., Everitt, B.J., Herbert, J., 1990. Comparative effects of preoptic area infusions Gropp,E.,Shanabrough,M.,Borok,E.,Xu,A.W.,Janoschek,R.,Buch,T.,Plum,L.,Balthasar,N., of opioid peptides, lesions and castration on sexual behaviour in male rats: studies Hampel, B., Waisman, A., Barsh, G.S., Horvath, T.L., Bruning, J.C., 2005. Agouti-related of instrumental behaviour, conditioned place preference and partner preference. peptide-expressing neurons are mandatory for feeding. Nat. Neurosci. 8, 1289–1291. Psychopharmacology 102, 243–256. Groscolas, R., Decrock, F., Thil, M.A., Fayolle, C., Boissery, C., Robin, J.P., 2000. Refeeding Humphries, M.M., Thomas, D.W., Kramer, D.L., 2003. Theroleofenergyavailabilityin signal in fasting-incubating king penguins: changes in behavior and egg temperature. Mammalian hibernation: a cost–benefit approach. Physiol. Biochem. Zool. 76, 165–179. Am. J. Physiol. Regul. Integr. Comp. Physiol. 279, R2104–R2112. Humphries, M.M., Umbanhowar, J., McCann, K.S., 2004. Bioenergetic prediction of climate Groscolas, R., Lacroix, A., Robin, J.P., 2008. Spontaneous egg or chick abandonment in energy- change impacts on northern mammals. Integr. Comp. Biol. 44, 152–162. depleted king penguins: a role for corticosterone and prolactin? Horm. Behav. 53, 51–60. Huo, L., Maeng, L., Bjorbaek, C., Grill, H.J., 2007. Leptin and the control of food intake: Gruaz, N.M., d'Alleves, V., Charnay, Y., Skotther, A., Ekvarn, S., Fryklund, L., Aubert, M.L., neurons in the nucleus of the solitary tract are activated by both gastric distension 1997. Effects of constant infusion with insulin-like growth factor-I (IGF-I) to imma- and leptin. Endocrinology 148, 2189–2197. ture female rats on body weight gain, tissue growth, and sexual function: evidence I'Anson, H., Foster, D.L., Foxcroft, C.R., Booth, P.J., 1991. Nutrition and reproduction. Oxf. that such treatment does not affect sexual maturation or fertility. Endocrine 6, 11–19. Rev. Reprod. Biol. 13, 239–311. Gualillo, O., Caminos, J.E., Nogueiras, R., Seoane, L.M., Arvat, E., Ghigo, E., Casanueva, F.F., I'Anson, H., Sundling, L.A., Roland, S.M., Ritter, S., 2003. Immunotoxic destruction of Dieguez, C., 2002. Effect of food restriction on ghrelin in normal-cycling female rats distinct catecholaminergic neuron populations disrupts the reproductive response and in pregnancy. Obes. Res. 10, 682–687. to glucoprivation in female rats. Endocrinology 144, 4325–4331. Gyengesi, E., Liu, Z.W., D'Agostino, G., Gan, G., Horvath, T.L., Gao, X.B., Diano, S., 2010. Ichimaru,T.,Matsuyama,S.,Ohkura,S.,Mori,Y.,Okamura,H.,2003.Central cholecystokinin- Corticosterone regulates synaptic input organization of POMC and NPY/AgRP neurons octapeptide accelerates the activity of the hypothalamic gonadotropin-releasing in adult mice. Endocrinology 151, 5395–5402. hormone pulse generator in goats.J.Neuroendocrinol.15,80–86. Halaas, J.L., Gajiwala, K.S., Maffei, M., Cohen, S.L., Chait, B.T., Rabinowitz, D., Lallone, R.L., Irwig, M.S., Fraley, G.S., Smith, J.T., Acohido, B.V., Popa, S.M., Cunningham, M.J., Burley, S.K., Friedman, J.M., 1995. Weight-reducing effects of the plasma protein Gottsch,M.L.,Clifton,D.K.,Steiner,R.A.,2004.Kisspeptin activation of gonado- encoded by the obese gene. Science 269, 543–546. tropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male Hall, T.R., Cheung, A., 1991. Galanin stimulates release of LH in young chickens. Horm. rat. Neuroendocrinology 80, 264–272. Metab. Res. 23, 570–571. Iwata, K., Kinoshita, M., Susaki, N., Uenoyama, Y., Tsukamura, H., Maeda, K., 2011. Central Halpern, M., Martínez-Marcos, A., 2003. Structure and function of the vomeronasal sys- injection of ketone body suppresses luteinizing hormone release via the catechol- tem: an update. Prog. Neurobiol. 70, 245–318. aminergic pathway in female rats. J. Reprod. Dev. 57, 379–384. Halpern, M., Schulman, N., Kirschenbaum, D.M., 1986. Characteristics of earthworm wash- Jaccoby, S., Arnon, E., Snapir, N., Robinzon, B., 1995. Effects of estradiol and tamoxifen ings detected by the vomeronasal system of snakes. In: Duvall, D., Müller-Schwarze, on feeding, fattiness, and some endocrine criteria in hypothalamic obese hens. D., Silverstein, R.M. (Eds.), Chemical Signals in Vertebrates 4: Ecology, Evolution, Pharmacol. Biochem. Behav. 50, 55–63. and Comparative Biology. Plenum, New York, pp. 63–77. Jaccoby, S., Pinchasov, Y., Snapir, N., Robinzon, B., 1996. Hypothalamic obese, functionally Hamelink, C.R., Currie, P.J., Chambers, J.W., Castonguay, T.W., Coscina, D.V., 1994. Cortico- castrated hens are hypersensitive to estrogenic modulation of lipid metabolism. sterone-responsive and -unresponsive metabolic characteristics of adrenalectomized Physiol. Behav. 60, 913–918. rats. Am. J. Physiol. 267, R799–R804. Jarmon, H., Gerall, A.A., 1961. The effect of food deprivation upon the sexual performance He, W., Lam, T.K., Obici, S., Rossetti, L., 2006. Molecular disruption of hypothalamic nutri- of male guinea pigs. J. Comp. Physiol. Psychol. 54, 306–309. ent sensing induces obesity. Nat. Neurosci. 9, 227–233. Ji, H., Friedman, M.I., 1999. Compensatory hyperphagia after fasting tracks recovery of Heffner, T.G., Zigmond, M.J., Stricker, E.M., 1977. Effects of dopaminergic agonists and liver energy status. Physiol. Behav. 68, 181–186. antagonists of feeding in intact and 6-hydroxydopamine-treated rats. J. Pharmacol. Ji, H., Graczyk-Milbrandt, G., Friedman, M.I., 2000. Metabolic inhibitors synergistically Exp. Ther. 201, 386–399. decrease hepatic energy status and increase food intake. Am. J. Physiol. Regul. Integr. Heine, P.A., Taylor, J.A., Iwamoto, G.A., Lubahn, D.B., Cooke, P.S., 2000. Increased adipose Comp. Physiol. 278, R1579–R1582. tissue in male and female estrogen receptor-alpha knockout mice. Proc. Natl. Acad. Johnson, R.P., 1973. Scent marking in mammals. Anim. Behav. 521–535. Sci. U.S.A. 97, 12729–127934. Johnson, M.A., Tsutsui, K., Fraley, G.S., 2007. Rat RFamide-related peptide-3 stimulates GH Heinen, J., 1994. Antipredator behavior of newly metamorphosed American toads (Bufo a. secretion, inhibits LH secretion, and has variable effects on sex behavior in the adult americanus), and mechanisms of hunting by eastern garter snakes (Thamnophis s. male rat. Horm. Behav. 51, 171–180. sirtalis). Herpetologica 50, 137–145. Johnston, R.E., 1974. Sexual attraction function of golden hamster vaginal secretion. Heinrichs, S.C., Richard, D., 1999. The role of corticotropin-releasing factor and urocortin Behav. Biol. 12, 111–117. in the modulation of ingestive behavior. Neuropeptides 33, 350–359. Johnston, R.E., 1975. Scent marking by male Golden Hamsters (Mesocricetus auratus)III. Hervey, E., Hervey, G.R., 1966. The relationship between the effects of ovariectomy Behavior in a seminatural environment. Z. Tierpsychol. 37, 213–221. and progesterone treatment on body weight and composition in the female rat. Johnston, R.E., 1977. The causation of two scent-marking behavior patterns in female J. Physiol. 187, 44P–45P. hamsters (Mesocricentus auratus). Anim. Behav. 25, 317–327. Hervey, E., Hervey, G.R., 1969. Energy storage in female rats treated with progesterone in Jonaidi, H., Oloumi, M.M., Denbow, D.M., 2003. Behavioral effects of intracerebroven- the absence of increased intake of food. J. Physiol. 200, 118P–119P. tricular injection of oxytocin in birds. Physiol. Behav. 79, 725–729. Hetherington, M.M., Stoner, S.A., Andersen, A.E., Rolls, B.J., 2000. Effects of acute food Jones, J.E., Pick, R.R., Davenport, M.D., Keene, A.C., Corp, E.S., Wade, G.N., 2002. Disinhibi- deprivation on eating behavior in eating disorders. Int. J. Eat. Disord. 28, 272–283. tion of female sexual behavior by a CRH receptor antagonist in Syrian hamsters. Am. Hiebert, S.M., Salvante, K.G., Ramenofsky, M., Wingfield, J.C., 2000. Corticosterone and noc- J. Physiol. Regul. Integr. Comp. Physiol. 283, R591–R597. turnal torpor in the rufous hummingbird (Selasphorus rufus). Gen. Comp. Endocrinol. Jones, J.E., Pick, R.R., Dettloff, S.L., Wade, G.N., 2004. Metabolic fuels, neuropeptide Y, and 120, 220–234. estrous behavior in Syrian hamsters. Brain Res. 1007, 78–85. Hileman, S.M., Schillo, K.K., Hall, J.B., 1993. Effects of acute, intracerebroventricular admin- Jonsson, E., 2013. The role of ghrelin in energy balance regulation in fish. Gen. Comp. istration of insulin on serum concentrations of luteinizing hormone, insulin, and glu- Endocrinol. 187C, 79–85. cose in ovariectomized lambs during restricted and ad libitum feed intake. Biol. Jonsson, E., Kaiya, H., Bjornsson, B.T., 2010. Ghrelin decreases food intake in juvenile rain- Reprod. 48, 117–124. bow trout (Oncorhynchus mykiss) through the central anorexigenic corticotropin- Hill, J.O., Fried, S.K., DiGirolamo, M., 1984. Effects of fasting and restricted refeeding on uti- releasing factor system. Gen. Comp. Endocrinol. 166, 39–46. lization of ingested energy in rats. Am. J. Physiol. 247, R318–R327. Kah, O., Trudeau, V.L., Sloley, B.D., Chang, J.P., Dubourg, P., Yu, K.L., Peter, R.E., 1992. Influ- Hill, J.W., Elmquist, J.K., Elias, C.F., 2008. Hypothalamic pathways linking energy balance ence of GABA on gonadotrophin release in the goldfish. Neuroendocrinology 55, and reproduction. Am. J. Physiol. Endocrinol. Metab. 294, E827–E832. 396–404. Himick, B.A., Peter, R.E., 1994. CCK/gastrin-like immunoreactivity in brain and gut, and Kaiya, H., Furuse, M., Miyazato, M., Kangawa, K., 2009. Current knowledge of the roles of CCK suppression of feeding in goldfish. Am. J. Physiol. 267, R841–R851. ghrelin in regulating food intake and energy balance in birds. Gen. Comp. Endocrinol. Hobbs, N.J., Finger, A.A., Ferkin, M.H., 2012. Effects of food availability on proceptivity: a 163, 33–38. test of the reproduction at all costs and metabolic fuels hypotheses. Behav. Processes Kang, K.S., Shimizu, K., Azuma, M., Ui, Y., Nakamura, K., Uchiyama, M., Matsuda, K., 2011. 91, 192–197. Gonadotropin-releasing hormone II (GnRH II) mediates the anorexigenic actions of 724 J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728

alpha-melanocyte-stimulating hormone (alpha-MSH) and corticotropin-releasing Kriegsfeld, L.J., Mei, D.F., Bentley, G.E., Ubuka, T., Mason, A.O., Inoue, K., Ukena, K., Tsutsui, hormone (CRH) in goldfish. Peptides 32, 31–35. K., Silver, R., 2006. Identification and characterization of a gonadotropin-inhibitory Kauffman, A.S., Rissman, E.F., 2004a. A critical role for the evolutionarily conserved system in the brains of mammals. Proc. Natl. Acad. Sci. U.S.A. 103, 2410–2415. gonadotropin-releasing hormone II: mediation of energy status and female sexual Kristensen, P., Judge, M.E., Thim, L., Ribel, U., Christjansen, K.N., Wulff, B.S., Clausen, J.T., behavior. Endocrinology 145, 3639–3646. Jensen, P.B., Madsen, O.D., 1998. Hypothalamic CART is a new anorectic peptide Kauffman, A.S., Rissman, E.F., 2004b. The evolutionarily conserved gonadotropin- regulated by leptin. Nature 72–76. releasing hormone II modifies food intake. Endocrinology 145, 686–691. Kronfeld-Schor, N., Richardson, C., Silvia, B.A., Kunz, T.H., Widmaier, E.P., 2000. Dissocia- Kauffman, A.S., Wills, A., Millar, R.P., Rissman, E.F., 2005. Evidence that the type-2 tion of leptin secretion and adiposity during prehibernatory fattening in little gonadotrophin-releasing hormone (GnRH) receptor mediates the behavioural effects brown bats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 279, R1277–R1281. of GnRH-II on feeding and reproduction in musk shrews. J. Neuroendocrinol. 17, Kubie, J.L., Halpern, M., 1975. Laboratory observations of trailing behavior in garter 489–497. snakes. J. Comp. Physiol. Psychol. 89, 667–674. Kauffman, A.S., Bojkowska, K., Wills, A., Rissman, E.F., 2006. Gonadotropin-releasing Kubota, N., Yano, W., Kubota, T., Yamauchi, T., Itoh, S., Kumagai, H., Kozono, H., Takamoto, hormone-II messenger ribonucleic acid and protein content in the mammalian I., Okamoto, S., Shiuchi, T., Suzuki, R., Satoh, H., Tsuchida, A., Moroi, M., Sugi, K., Noda, brain are modulated by food intake. Endocrinology 147, 5069–5077. T., Ebinuma, H., Ueta, Y., Kondo, T., Araki, E., Ezaki, O., Nagai, R., Tobe, K., Terauchi, Y., Kavaliers, M., Hirst, M., 1986. Food hoarding and ingestion in the deer mouse, Peromyscus Ueki, K., Minokoshi, Y., Kadowaki, T., 2007. Adiponectin stimulates AMP-activated maniculatus: selective responses to mu and kappa opiate agonists. Pharmacol. protein kinase in the hypothalamus and increases food intake. Cell Metab. 6, 55–68. Biochem. Behav. 25, 543–548. Kyrkouli, S.E., Stanley, B.G., Seirafi, R.D., Leibowitz, S.F., 1990. Stimulation of feeding by Kawakami, S., Bungo, T., Ando, R., Ohgushi, A., Shimojo, M., Masuda, Y., Furuse, M., 2000. galanin: anatomical localization and behavioral specificity of this peptide's effects Central administration of alpha-melanocyte stimulating hormone inhibits fasting- in the brain. Peptides 11, 995–1001. and neuropeptide Y-induced feeding in neonatal chicks. Eur. J. Pharmacol. 398, la Fleur, S.E., Ji, H., Manalo, S.L., Friedman, M.I., Dallman, M.F., 2003. The hepatic vagus 361–364. mediates fat-induced inhibition of diabetic hyperphagia. Diabetes 52, 2321–2330. Keene, A.C., Jones, J.E., Wade, G.N., Corp, E.S., 2003. Forebrain sites of NPY action on estrous Lack, D.L., 1954. The Natural Regulation of Animal Numbers. Oxford University Press, behavior in Syrian hamsters. Physiol. Behav. 78, 711–716. Oxford. Keen-Rhinehart, E., Bartness, T.J., 2005. Peripheral ghrelin injections stimulate food intake, Lack, D.L., 1968. Ecological Adaptations for Breeding in Birds. Metheun, London. foraging, and food hoarding in Siberian hamsters. Am. J. Physiol. Regul. Integr. Comp. Lagaly, D.V., Aad, P.Y., Grado-Ahuir, J.A., Hulsey, L.B., Spicer, L.J., 2008. Role of adiponectin in Physiol. 288, R716–R722. regulating ovarian theca and granulosa cell function. Mol. Cell. Endocrinol. 284, 38–45. Keen-Rhinehart, E., Bartness, T.J., 2007a. MTII attenuates ghrelin- and food deprivation- Lazzarini, S.J., Schneider, J.E., Wade, G.N., 1988. Inhibition of fatty acid oxidation and induced increases in food hoarding and food intake. Horm. Behav. 52, 612–620. glucose metabolism does not affect food intake or hunger motivation in Syrian ham- Keen-Rhinehart, E., Bartness, T.J., 2007b. NPY Y1 receptor is involved in ghrelin- and sters. Physiol. Behav. 44, 209–213. fasting-induced increases in foraging, food hoarding, and food intake. Am. J. Physiol. Le Boeuf, B.J., Laws, R.M., 1994. Elephant Seals: Population Ecology, Behavior and Physiol- Regul. Integr. Comp. Physiol. 292, R1728–R1737. ogy. University of California Press, Berkeley, California. Keen-Rhinehart, E., Bartness, T.J., 2008. Leptin inhibits food-deprivation-induced increases Leal, E., Sanchez, E., Muriach, B., Cerda-Reverter, J.M., 2009. Sex steroid-induced inhibition in food intake and food hoarding. Am. J. Physiol. Regul. Integr. Comp. Physiol. 295, of food intake in sea bass (Dicentrarchus labrax). J. Comp. Physiol. B Biochem. Syst. R1737–R1746. Environ. Physiol. 179, 77–86. Kelley, A.E., Stinus, L., 1985. Disappearance of hoarding behavior after 6-hydroxydopamine Leal, E., Fernandez-Duran, B., Agulleiro, M.J., Conde-Siera, M., Miguez, J.M., Cerda-Reverter, lesions of the mesolimbic dopamine neurons and its reinstatement with L-dopa. J.M., 2013. Effects of dopaminergic system activation on feeding behavior and growth Behav. Neurosci. 99, 531–545. performance of the sea bass (Dicentrarchus labrax): a self-feeding approach. Horm. Khatib, F.A., Shafagoj, Y.A., 2004. Metabolic alterations as a result of Ramadan fasting in Behav. 64, 113–121. non-insulin-dependent diabetes mellitus patients in relation to food intake. Saudi Lebrethon, M.C., Vandersmissen, E., Gerard, A., Parent, A.S., Bourguignon, J.P., 2000. Med. J. 25, 1858–1863. Cocaine and amphetamine-regulated-transcript peptide mediation of leptin stimula- Kim, T.W., Sakamotom, K., Henmi, Y., Choe, J.C., 2008. To court or not to court: reproduc- tory effect on the rat gonadotropin-releasing hormone pulse generator in vitro. tive decisions by male fiddler crabs in response to fluctuating food availability. Behav. J. Neuroendocrinol. 12, 383–385. Ecol.Sociobiol.62,1139–1147. Leibowitz, S.F., Alexander, J.T., 1991. Analysis of neuropeptide Y-induced feeding: dissoci- Kimura, F., Hashimoto, R., Kawakami, M., 1983. The stimulatory effect of cholecystokinin ation of Y1 and Y2 receptor effects on natural meal patterns. Peptides 12, 1251–1260. implanted in the medial preoptic area on luteinizing hormone secretion in the ovari- LeMaster, M.P., Mason, R.T., 2001. Evidence for a female sex pheromone mediating male ectomized estrogen-primed rat. Endocrinol. Jpn. 30, 305–309. trailing behavior in the red-sided garter snake, Thamnophis sirtalis parietalis. Kinzeler, N.R., Travers, S.P., 2008. Licking and gaping elicited by microstimulation of the Chemoecology 11, 149–152. nucleusofthesolitarytract.Am.J.Physiol.Regul.Integr.Comp.Physiol.295,R436–R448. LeMaster, M.P., Mason, R.T., 2002. Variation in a female sexual attractiveness pheromone Kirk, K.L., 1997. Life-history responses to variable environments: starvation and reproduc- controls male mate choice in garter snakes. J. Chem. Ecol. 28, 1269–1285. tion in planktonic rotifers. Ecology 78, 434–441. Levine, A.S., Rogers, B., Kneip, J., Grace, M., Morley, J.E., 1983. Effect of centrally adminis- Kitaysky, A.S., Kitaiskaia, E.V., Wingfield, J.C., Piatt, J.F., 2001. Dietary restriction causes tered corticotropin releasing factor (CRF) on multiple feeding paradigms. Neurophar- chronic elevation of corticosterone and enhances stress response in red-legged macology 22, 337–339. kittiwake chicks. J. Comp. Physiol. B Biochem. Syst. Environ. Physiol. 171, 701–709. Li, H.-Y., Wade, G.N., Blaustein, J.D., 1994. Manipulations of metabolic fuel availability alter Klingerman, C.M., Krishnamoorthy, K., Patel, K., Spiro, A.B., Struby, C., Patel, A., Schneider, estrous behavior and neural estrogen-receptor immunoreactivity in Syrian hamsters. J.E., 2010. Energetic challenges unmask the role of ovarian hormones in orchestrating Endocrinology 135, 240–247. ingestive and sex behaviors. Horm. Behav. 58, 563–574. Li, X.F., Bowe, J.E., Lightman, S.L., O'Byrne, K.T., 2005. Role of corticotropin-releasing factor Klingerman, C.M., Patel, A., Hedges, V.L., Meisel, R.L., Schneider, J.E., 2011a. Food re- receptor-2 in stress-induced suppression of pulsatile luteinizing hormone secretion striction dissociates sexual motivation, sexual performance, and the rewarding in the rat. Endocrinology 146, 318–322. consequences of copulation in female Syrian hamsters. Behav. Brain Res. 223, Li, A.J., Wang, Q., Ritter, S., 2011. Participation of hindbrain AMP-activated protein kinase 356–370. in glucoprivic feeding. Diabetes 60, 436–442. Klingerman, C.M., Williams III, W.P., Simberlund, J., Brahme, N., Prasad, A., Schneider, J.E., Licht, P., Millar, R., King, J.A., McCreery, B.R., Mendonca, M.T., Bona-Gallo, A., Lofts, B., 1984. Kriegsfeld, L.J., 2011b. Food restriction-induced changes in gonadotropin-inhibiting Effects of chicken and mammalian gonadotropin-releasing hormones (GnRH) on hormone cells are associated with changes in sexual motivation and food hoarding, in vivo pituitary gonadotropin release in amphibians and reptiles. Gen. Comp. but not sexual performance and food intake. Front. Endocrinol. 2, 101. Endocrinol. 54, 89–96. Klump, K.L., Gobrogge, K.L., Perkins, P.S., Thorne, D., Sisk, C.L., Marc Breedlove, S., 2006. Licht, P., Khorrami-Yaghoobi, P., Porter, D.A., 1985. Effects of gonadectomy and steroid Preliminary evidence that gonadal hormones organize and activate disordered eat- treatment on plasma gonadotropins and the response of superfused pituitaries to ing. Psychol. Med. 36, 539–546. gonadotropin-releasing hormone in the turtle Sternotherus odoratus.Gen.Comp. Koh, T., Nakai, Y., Kinoshita, F., Tsukada, T., Tsujii, S., Imura, H., Maeda, K., 1984. Serotonin Endocrinol. 60, 441–449. involvement in the inhibition of luteinizing hormone (LH) release during immobili- Liley, N.R., 1972. The effects of estrogens and other steroids on the sexual behavior of the zation in castrated male rats. Life Sci. 34, 1635–1641. female guppy, Poecilia reticulata. Gen. Comp. Endocrinol. 3, 542–552. Kohno, D., Sone, H., Tanaka, S., Kurita, H., Gantulga, D., Yada, T., 2011. AMP-activated pro- Lin, X., Volkoff, H., Narnaware, Y., Bernier, N.J., Peyon, P., Peter, R.E., 2000. Brain regulation tein kinase activates neuropeptide Y neurons in the hypothalamic arcuate nucleus to of feeding behavior and food intake in fish. Comp. Biochem. Physiol. A Mol. Integr. increase food intake in rats. Neurosci. Lett. 499, 194–198. Physiol. 126, 415–434. Kotz, C.M., Briggs, J.E., Pomonis, J.D., Grace, M.K., Levine, A.S., Billington, C.J., 1998. Neural Lindstrom, J., Pike, T.W., Blount, J.D., Metcalfe, N.B., 2009. Optimization of resource allocation site of leptin influence on neuropeptide Y signaling pathways altering feeding and can explain the temporal dynamics and honesty of sexual signals. Am. Nat. 174, 515–525. uncoupling protein. Am. J. Physiol. 275, R478–R484. Lipton, J., Kleemann, G., Ghosh, R., Lints, R., Emmons, S.W., 2004. Mate searching in Kovacs, P., Morales, J.C., Karkanias, G.B., 2003. Central insulin administration maintains Caenorhabditis elegans: a genetic model for sex drive in a simple invertebrate. reproductive behavior in diabetic female rats. Neuroendocrinology 78, 90–95. J. Neurosci. Off. J. Soc. Neurosci. 24, 7427–7434. Kow, L.M., Pfaff, D.W., 2004. The membrane actions of estrogens can potentiate their lordosis Lisk, R.D., Ciaccio, L.A., Catanzaro, C., 1983. Mating behavior of the golden hamster under behavior-facilitating genomic actions. Proc. Natl. Acad. Sci. U.S.A. 101, 12354–12357. seminatural conditions. Anim. Behav. 31, 659–666. Kowalski, T.J., Farley, C., Cohen-Williams, M.E., Varty, G., Spar, B.D., 2004. Melanin-concen- Loiseau, C., Fellous, S., Haussy, C., Chastel, O., Sorci, G., 2008. Condition-dependent effects trating hormone-1 receptor antagonism decreases feeding by reducing meal size. Eur. of corticosterone on a carotenoid-based begging signal in house sparrows. Horm. J. Pharmacol. 497, 41–47. Behav. 53, 266–273. Krasnow, S.M., Fraley, G.S., Schuh, S.M., Baumgartner, J.W., Clifton, D.K., Steiner, R.A., 2003. Lopez-Patino, M.A., Guijarro, A.I., Isorna, E., Delgado, M.J., Alonso-Bedate, M., de Pedro, N., A role for galanin-like peptide in the integration of feeding, body weight regulation, 1999. Neuropeptide Y has a stimulatory action on feeding behavior in goldfish and reproduction in the mouse. Endocrinology 144, 813–822. (Carassius auratus). Eur. J. Pharmacol. 377, 147–153. J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 725

Lorenz, K., 1950. The comparative method in studying innate behavior patterns. Symp. Meyerson, B.J., Lindstrom, L.H., 1973. Sexual motivation in the female rat. A methodolog- Soc. Exp. Biol. 1950, 221–268. ical study applied to the investigation of the effect of estradiol benzoate. Acta Physiol. Lu,H.,Martinez-Nieves,B.,Lapanowski,K.,Dunbar,J.,2001.Intracerebroventricular Scand. Suppl. 389, 1–80. insulin-like growth factor-1 decreases feeding in diabetic rats. Endocrine 14, Michel, C., Cabanac, M., 1999. Effects of dexamethasone on the body weight set point of 349–352. rats. Physiol. Behav. 68, 145–150. Lu, M., Tang, Q., Olefsky, J.M., Mellon, P.L., Webster, N.J., 2008. Adiponectin activates aden- Milla, S., Wang, N., Mandiki, S.N., Kestemont, P., 2009. Corticosteroids: friends or foes osine monophosphate-activated protein kinase and decreases luteinizing hormone of teleost fish reproduction? Comp. Biochem. Physiol. A Mol. Integr. Physiol. 153, secretion in LbetaT2 gonadotropes. Mol. Endocrinol. 22, 760–771. 242–251. Luedtke, S., O'Connor, V., Holden-Dye, L., Walker, R.J., 2010. The regulation of feeding and Miller, D.W., Blache, D., Martin, G.B., 1995. The role of intracerebral insulin in the effect metabolism in response to food deprivation in Caenorhabditis elegans.Invert. of nutrition on gonadotropin secretion in mature male sheep. J. Endocrinol. 147, Neurosci. 10, 63–76. 321–329. Luquet, S., Perez, F.A., Hnasko, T.S., Palmiter, R.D., 2005. NPY/AgRP neurons are essential Minokoshi, Y., Shiuchi, T., Lee, S., Suzuki, A., Okamoto, S., 2008. Role of hypothalamic AMP- for feeding in adult mice but can be ablated in neonates. Science 310, 683–685. kinase in food intake regulation. Nutrition 24, 786–790. Luquet, S., Phillips, C.T., Palmiter, R.D., 2007. NPY/AgRP neurons are not essential for feed- Mitchell, J.B., Stewart, J., 1990. Facilitation of sexual behaviors in the male rat associated ing responses to glucoprivation. Peptides 28, 214–225. with intra-VTA injections of opiates. Pharmacol. Biochem. Behav. 35, 643–650. Lutterschmidt, D.I., LeMaster, M.P., Mason, R.T., 2004. Effects of melatonin on the behavioral Mitchell, B., McCowan, I.A., Nicholson, J., 1976. J. Zool. 180, 107. and hormonal responses of red-sided garter snakes (Thamnophis sirtalis parietalis)to Moenter, S.M., DeFazio, R.A., 2005. Endogenous gamma-aminobutyric acid can excite exogenous corticosterone. Horm. Behav. 46, 692–702. gonadotropin-releasing hormone neurons. Endocrinology 146, 5374–5379. Lutterschmidt, D.I., McHenry, S.D., Wilczynski, W., 2011. Inhibition of corticosterone syn- Moore, I.T., Jessop, T.S., 2003. Stress, reproduction, and adrenocortical modulation in thesis induces the transition from courtship to feeding behavior in red-sided garter amphibians and reptiles. Horm. Behav. 43, 39–47. snakes (Thamnophis sirtalis). Front. Endocrin. Conference Abstract: NASCE 2011, Moore, F.L., Zoeller, R.T., 1985. Stress-induced inhibition of reproduction: evidence The inaugural meeting of the North American Society for Comparative Endocrinology. of suppressed secretion of LH–RH in an amphibian. Gen. Comp. Endocrinol. 60, Front. Endocrinol. 252–258. Lyons, A.M., Thiele, T.E., 2010. Neuropeptide Y conjugated to saporin alters anxiety-like Morley, J.E., Levine, A.S., 1982. Corticotrophin releasing factor, grooming and ingestive behavior when injected into the central nucleus of the amygdala or basomedial hypo- behavior. Life Sci. 31, 1459–1464. thalamus in BALB/cJ mice. Peptides 31, 2193–2199. Morris, Y.A., Crews, D., 1990. The effects of exogenous neuropeptide Y on feeding and Mahler, S.V., Berridge, K.C., 2009. Which cue to “want?” Central amygdala opioid activation sexual behavior in the red-sided garter snake (Thamnophis sirtalis parietalis). Brain enhances and focuses incentive salience on a prepotent reward cue. J. Neurosci. Off. Res. 530, 339–341. J. Soc. Neurosci. 29, 6500–6513. Moss, R.L., McCann, S.M., 1975. Action of luteinizing hormone-releasing factor (lrf) in Maillard, V., Froment, P., Rame, C., Uzbekova, S., Elis, S., Dupont, J., 2011. Expression and the initiation of lordosis behavior in the estrone-primed ovariectomized female rat. effect of resistin on bovine and rat granulosa cell steroidogenesis and proliferation. Neuroendocrinology 17, 309–318. Reproduction 141, 467–479. Mota-Ortiz, S.R., Sukikara, M.H., Bittencourt, J.C., Baldo, M.V., Elias, C.F., Felicio, L.F., Makimura, H., Mizuno, T.M., Isoda, F., Beasley, J., Silverstein, J.H., Mobbs, C.V., 2003. Role Canteras, N.S., 2012. The periaqueductal gray as a critical site to mediate reward of glucocorticoids in mediating effects of fasting and diabetes on hypothalamic seeking during predatory hunting. Behav. Brain Res. 226, 32–40. gene expression. BMC Physiol. 3, 5. Mousa, S.A., Mousa, M.A., 2006. Involvement of corticotropin-releasing factor and adreno- Maney, D.L., Wingfield, J.C., 1998. Central opioid control of feeding behavior in the white- corticotropic hormone in the ovarian maturation, seawater acclimation, and induced crowned sparrow, Zonotrichia leucophrys gambelii. Horm. Behav. 33, 16–22. spawning of Liza ramada. Gen. Comp. Endocrinol. 146, 167–179. Mann, D.R., Evans, D., Edoimioya, F., Kamel, F., Butterstein, G.M., 1985. A detailed exami- Moussavi, M., Wlasichuk, M., Chang, J.P., Habibi, H.R., 2012. Seasonal effect of GnIH on nation of the in vivo and in vitro effects of ACTH on gonadotropin secretion in the gonadotrope functions in the pituitary of goldfish. Mol. Cell. Endocrinol. 350, 53–60. adult rat. Neuroendocrinology 40, 297–302. Muoio, D.M., Dohm, G.L., Fiedorek Jr., F.T., Tapscott, E.B., Coleman, R.A., 1997. Leptin Markham, M.R., Allee, S.J., Goldina, A., Stoddard, P.K., 2009. Melanocortins regulate the directly alters lipid partitioning in skeletal muscle. Diabetes 46, 1360–1363. electric waveforms of gymnotiform electric fish. Horm. Behav. 55, 306–313. Murashita, K., Uji, S., Yamamoto, T., Ronnestad, I., Kurokawa, T., 2008. Production of Mason, P., Adkins, E.K., 1976. Hormones and social behavior in the lizard, Anolis carolinensis. recombinant leptin and its effects on food intake in rainbow trout (Oncorhynchus Horm.Behav.7,75–86. mykiss). Comp. Biochem. Physiol. B Biochem. Mol. Biol. 150, 377–384. Mason, R.T., Fales, H.M., Jones, T.H., Pannell, L.K., Chinn, J.W., Crews, D., 1989. Sex phero- Musatov, S., Chen, W., Pfaff, D.W., Mobbs, C.V., Yang, X.J., Clegg, D.J., Kaplitt, M.G., Ogawa, mones in snakes. Science 245, 290–293. S., 2007. Silencing of estrogen receptor alpha in the ventromedial nucleus of hypo- Mason, R.T., Jones, T.H., Fales, H.M., Pannell, L.K., Crews, D., 1990. Characterization, synthe- thalamus leads to metabolic syndrome. Proc. Natl. Acad. Sci. U.S.A. 104, 2501–2506. sis, and behavioral responses to sex attractiveness pheromones of red-sided garter Myerson, B.J., Lindstrom, L., Nordstrom, E.B., Agmo, A., 1973. Sexual motivation in the snakes (Thamnophis sirtalis parietalis). J. Chem. Ecol. 16, 2353–2369. female rat after testosterone treatment. Physiol. Behav. 11, 421–428. Matsuda,K.,Kojima,K.,Shimakura,S.,Wada,K.,Maruyama,K.,Uchiyama,M.,Kikuyama,S., Nagatani, S., Thompson, R.C., Foster, D.L., 2001. Prevention of glucoprivic stimulation Shioda, S., 2008. Corticotropin-releasing hormone mediates alpha-melanocyte- of corticosterone secretion by leptin does not restore high frequency luteinizing stimulating hormone-induced anorexigenic action in goldfish. Peptides 29, 1930–1936. hormone pulses in rats. J. Neuroendocrinol. 13, 371–377. Matsumoto, H., Noguchi, J., Takatsu, Y., Horikoshi, Y., Kumano, S., Ohtaki, T., Kitada, C., Nasse, J., Terman, D., Venugopal, S., Hermann, G., Rogers, R., Travers, J.B., 2008. Local Itoh, T., Onda, H., Nishimura, O., Fujino, M., 2001. Stimulation effect of galanin-like circuit input to the medullary reticular formation from the rostral nucleus of the peptide (GALP) on luteinizing hormone-releasing hormone-mediated luteinizing solitary tract. Am. J. Physiol. Regul. Integr. Comp. Physiol. 295, R1391–R1408. hormone (LH) secretion in male rats. Endocrinology 142, 3693–3696. Negri, L., Noviello, L., Noviello, V., 1985. Effects of sauvagine, urotensin I and CRF on food Matsumoto, Y., Watanabe, T., Adachi, Y., Itoh, T., Ohtaki, T., Onda, H., Kurokawa, T., intake in rats. Peptides 6 (Suppl. 3), 53–57. Nishimura, O., Fujino, M., 2002. Galanin-like peptide stimulates food intake in the Nelson, L.E., Sheridan, M.A., 2006. Gastroenteropancreatic hormones and metabolism in rat. Neurosci. Lett. 322, 67–69. fish. Gen. Comp. Endocrinol. 148, 116–124. McCreery, B.R., Licht, P., 1984. Effects of gonadectomy and sex steroids on pituitary Nemoto, T., Iwasaki-Sekino, A., Yamauchi, N., Shibasaki, T., 2010. Role of urocortin 2 gonadotrophin release and response to gonadotrophin-releasing hormone (GnRH) secreted by the pituitary in the stress-induced suppression of luteinizing hormone agonist in the bullfrog, Rana catesbeiana. Gen. Comp. Endocrinol. 54, 283–296. secretion in rats. Am. J. Physiol. Endocrinol. Metab. 299, E567–E575. McDevitt, M.A., Glidewell-Kenney, C., Weiss, J., Chambon, P., Jameson, J.L., Levine, J.E., Nir, I., Levy, V., 1973. Response of blood plasma glucose, free fatty acids, triglycerides, 2007. Estrogen response element-independent estrogen receptor (ER)-alpha signal- insulin and food intake to bovine insulin in geese and cockerels. Poult. Sci. 52, 886–892. ing does not rescue sexual behavior but restores normal testosterone secretion in Nishiguchi, R., Azuma, M., Yokobori, E., Uchiyama, M., Matsuda, K., 2012. Gonadotropin- male ERalpha knockout mice. Endocrinology 148, 5288–5294. releasing hormone 2 suppresses food intake in the zebrafish, Danio rerio. Front. McDevitt, M.A., Glidewell-Kenney, C., Jimenez, M.A., Ahearn, P.C., Weiss, J., Jameson, J.L., Endocrinol. 3, 122. Levine, J.E., 2008. New insights into the classical and non-classical actions of estrogen: Nock, B., Feder, H.H., 1979. Noradrenergic transmission and female sexual behavior of evidence from estrogen receptor knock-out and knock-in mice. Mol. Cell. Endocrinol. guinea pigs. Brain Res. 166, 369–380. 290, 24–30. Nunes, S., Pelz, K.M., Muecke, E.M., Holekamp, K.E., Zucker, I., 2006. Plasma glucocorticoid McDonald, P.G., Meyerson, B.J., 1973. The effect of oestradiol, testosterone and dihydro- concentrations and body mass in ground squirrels: seasonal variation and circannual testosterone on sexual motivation in the ovariectomized female rat. Physiol. Behav. organization. Gen. Comp. Endocrinol. 146, 136–143. 11, 515–520. Nunez, A.A., Gray, J.M., Wade, G.N., 1980. Food intake and adipose tissue lipoprotein lipase McKay, L.D., Kenney, N.J., Edens, N.K., Williams, R.H., Woods, S.C., 1981. Intracerebroven- activity after hypothalamic estradiol benzoate implants in rats. Physiol. Behav. 25, 595–598. tricular beta-endorphin increases food intake of rats. Life Sci. 29, 1429–1434. O'Connor, C.M., Gilmour, K.M., Arlinghaus, R., Van Der Kraak, G., Cooke, S.J., 2009. Stress McLaughlin, C.L., Stern, J.S., Baile, C.A., 1987. Weight gain and food intake in corticotropin and parental care in a wild Teleost fish: insights from exogenous supraphysiological releasing factor immunized Zucker rats. Physiol. Behav. 41, 171–178. cortisol implants. Physiol. Biochem. Zool. 82, 709–719. Meisel, R.L., Mullins, A.J., 2006. Sexual experience in female rodents: cellular mechanisms O'Donnell, R.P., Shine, R., Mason, R.T., 2004. Seasoal anorexia in the male red-sided garter and functional consequences. Brain Res. 1126, 56–65. snake, Thamnophis sirtalis parietalis. Behav. Ecol. Sociobiol. 56, 413–419. Mela, D.J., Aaron, J.I., Gatenby, S.J., 1996. Relationships of consumer characteristics and Ohlsson, C., Hellberg, N., Parini, P., Vidal, O., Bohlooly, M., Rudling, M., Lindberg, M.K., food deprivation to food purchasing behavior. Physiol. Behav. 60, 1331–1335. Warner, M., Angelin, B., Gustafsson, J.A., 2000. Obesity and disturbed lipoprotein pro- Mendelson, S.D., Gorzalka, B.B., 1984. Cholecystokinin-octapeptide produces inhibition of file in estrogen receptor-alpha-deficient male mice. Biochem. Biophys. Res. Commun. lordosis in the female rat. Physiol. Behav. 21, 755–759. 278, 640–645. Meredith, S., Kirkpatrick-Keller, D., Butcher, R.L., 1986. The effects of food restriction and Olofsson, L.E., Unger, E.K., Cheung, C.C., Xu, A.W., 2013. Modulation of AgRP-neuronal hypophysectomy on numbers of primordial follicles and concentrations of hormones function by SOCS3 as an initiating event in diet-induced hypothalamic leptin resis- in rats. Biol. Reprod. 35, 68–73. tance. Proc. Natl. Acad. Sci. U.S.A. 110, E697–E706. 726 J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728

Olson, B.R., Drutarosky, M.D., Stricker, E.M., Verbalis, J.G., 1991. Brainoxytocinrecep- Quesada, A., Etgen, A.M., 2002. Functional interactions between estrogen and insulin-like tors mediate corticotropin-releasing hormone-induced anorexia. Am. J. Physiol. growth factor-I in the regulation of alpha 1B-adrenoceptors and female reproductive 260, R448–R452. function. J. Neurosci. Off. J. Soc. Neurosci. 22, 2401–2408. Olster, D.H., Ferin, M., 1987. Corticotropin-releasing hormone inhibits gonadotropin Rawson, N.E., Ji, H., Friedman, M.I., 2003. 2,5-Anhydro-D-mannitol increases hepatocyte secretion in the ovariectomized rhesus monkey. J. Clin. Endocrinol. Metab. 65, 262–267. calcium: implications for a hepatic hunger stimulus. Biochim. Biophys. Acta 1642, Omeljaniuk, R.J., Tonon, M.C., Peter, R.E., 1989. Dopamine inhibition of gonadotropin and 59–66. alpha-melanocyte-stimulating hormone release in vitro from the pituitary of the Redshaw, M.R., Follett, B.K., Nichollis, T.J., 1969. Comparative effects of the oestrogens and goldfish (Carassius auratus). Gen. Comp. Endocrinol. 74, 451–467. other steroid hormones on serum lipids and proteins in Xenopus laevis Daudin. Osgood, W.H., Preble, E.A., Parker, G.H., 1914. The Fur Seals and Other Life of the Pribilof J. Endocrinol. 43, 47–53. Islands, Alaska, in 1914. Rettori, V., Canteros, G., Renoso, R., Gimeno, M., McCann, S.M., 1997. Oxytocin stimu- Paczoska-Eliasiewicz, H.E., Gertler,A.,Proszkowiec,M.,Proudman,J.,Hrabia,A.,Sechman,A., lates the release of luteinizing hormone-releasing hormone from medial basal Mika, M., Jacek, T., Cassy, S., Raver, N., Rzasa, J., 2003. Attenuation by leptin of the effects of hypothalamic explants by releasing nitric oxide. Proc. Natl. Acad. Sci. U.S.A. 94, fasting on ovarian function in hens (Gallus domesticus). Reproduction 126, 739–751. 2741–2744. Palin, M.F., Bordignon, V.V., Murphy, B.D., 2012. Adiponectin and the control of female Rissman, E.F., Wersinger, S.R., Taylor, J.A., Lubahn, D.B., 1997. Estrogen receptor function reproductive functions. Vitam. Horm. 90, 239–287. as revealed by knockout studies: neuroendocrine and behavioral aspects. Horm. Parent, A.S., Lebrethon, M.C., Gerard, A., Vandersmissen, E., Bourguignon, J.P., 2000. Leptin Behav. 31, 232–243. effects on pulsatile gonadotropin releasing hormone secretion from the adult rat Riters, L.V., Absil, P., Balthazart, J., 1999. Effects of naloxone on the acquisition and expres- hypothalamus and interaction with cocaine and amphetamine regulated transcript sion of appetitive and consummatory sexual behavior in male Japanese quail. Physiol. peptide and neuropeptide Y. Regul. Pept. 92, 17–24. Behav. 66, 763–773. Park, C.J., Zhao, Z., Glidewell-Kenney, C., Lazic, M., Chambon, P., Krust, A., Weiss, J., Clegg, Ritter, S., 1986. Glucoprivation and the glucoprivic control of food intake. Feeding Behav- D.J., Dunaif, A., Jameson, J.L., Levine, J.E., 2011. Genetic rescue of nonclassical ERalpha ior Neural and Humoral Controls.Academic Press, Inc. 271–303. signaling normalizes energy balance in obese Eralpha-null mutant mice. J. Clin. Ritter, R.C., Epstein, A.N., 1975. Control of meal size by central noradrenergic action. Proc. Invest. 121, 604–612. Natl. Acad. Sci. U.S.A. 72, 3740–3743. Paul, M.J., Galang, J., Schwartz, W.J., Prendergast, B.J., 2009a. Intermediate-duration day Rivier, C.L., 2008. Urocortin 1 inhibits rat Leydig cell function. Endocrinology 149, lengths unmask reproductive responses to nonphotic environmental cues. Am. 6425–6432. J. Physiol. Regul. Integr. Comp. Physiol. 296, R1613–R1619. Roa, J., Garcia-Galiano, D., Varela, L., Sanchez-Garrido, M.A., Pineda, R., Castellano, J.M., Paul, M.J., Pyter, L.M., Freeman, D.A., Galang, J., Prendergast, B.J., 2009b. Photic and nonphotic Ruiz-Pino, F., Romero, M., Aguilar, E., Lopez, M., Gaytan, F., Dieguez, C., Pinilla, L., seasonal cues differentially engage hypothalamic kisspeptin and RFamide-related pep- Tena-Sempere, M., 2009. The mammalian target of rapamycin as novel central regu- tide mRNA expression in Siberian hamsters. J. Neuroendocrinol. 21, 1007–1014. lator of puberty onset via modulation of hypothalamic Kiss1 system. Endocrinology Pelleymounter, M., Cullen, M., Baker, M., Hecht, R., Winters, D., Boone, T., Collins, F., 1995. 150, 5016–5026. Effects of the obese gene product on body weight regulation in ob/ob mice. Science Robin, J.P., Boucontet, L., Chillet, P., Groscolas, R., 1998. Behavioral changes in fasting 269, 540–543. emperor penguins: evidence for a “refeeding signal” linked to a metabolic shift. Peng, C., Trudeau, V.L., Peter, R.E., 1993. Seasonal variation of neuropeptide Y actions on Am. J. Physiol. 274, R746–R753. growth hormone and gonadotropin-II secretion in the goldfish: effects of sex steroids. Roepke, T.A., Bosch, M.A., Rick, E.A., Lee, B., Wagner, E.J., Seidlova-Wuttke, D., Wuttke, W., J. Neuroendocrinol. 5, 273–280. Scanlan, T.S., Ronnekleiv, O.K., Kelly, M.J., 2010. Contribution of a membrane estrogen Perello, M., Scott, M.M., Sakata, I., Lee, C.E., Chuang, J.C., Osborne-Lawrence, S., Rovinsky, receptor to the estrogenic regulation of body temperature and energy homeostasis. S.A., Elmquist, J.K., Zigman, J.M., 2012. Functional implications of limited leptin recep- Endocrinology 151, 4926–4937. tor and ghrelin receptor coexpression in the brain. J. Comp. Neurol. 520, 281–294. Roney, J.R., Simmons, Z.L., 2013. Hormonal predictors of sexual motivation in natural Perera, A.D., Verbalis, J.G., Mikuma, N., Majumdar, S.S., Plant, T.M., 1993. Cholecystokinin menstrual cycles. Horm. Behav. 63, 636–645. stimulates gonadotropin-releasing hormone release in the monkey (Macaca mulatta). Root, A.W., Reiter, E.O., Duckett, G.E., Sweetland, M.L., 1975. Effect of short-term Endocrinology 132, 1723–1728. castration and starvation upon hypothalamic content of luteinizing hormone- Perfito, N., Kwong, J.M., Bentley, G.E., Hau, M., 2008. Cue hierarchies and testicular releasing hormone in adult male rats. Proc. Soc. Exp. Biol. Med. Soc. Exp. Biol. development: is food a more potent stimulus than day length in an opportu- Med. 150, 602–605. nistic breeder (Taeniopygia g. guttata)? Horm. Behav. 53, 567–572. Rossetti, L., Massillon, D., Barzilai, N., Vuguin, P., Chen, W., Hawkins, M., Wu, J., Wang, J., Peyon, P., Zanuy, S., Carrillo, M., 2001. Action of leptin on in vitro luteinizing hormone 1997. Short term effects of leptin on hepatic gluconeogenesis and in vivo insulin release in the European sea bass (Dicentrarchus labrax). Biol. Reprod. 65, action. J. Biol. Chem. 272, 27758–27763. 1573–1578. Rossi, M., Kim, M.S., Morgan, D.G., Small, C.J., Edwards, C.M., Sunter, D., Abusnana, S., Peyon, P., Vega-Rubin de Celis, S., Gomez-Requeni, P., Zanuy, S., Perez-Sanchez, J., Carrillo, Goldstone, A.P., Russell, S.H., Stanley, S.A., Smith, D.M., Yagaloff, K., Ghatei, M.A., M., 2003. In vitro effect of leptin on somatolactin release in the European sea bass Bloom, S.R., 1998. A C-terminal fragment of Agouti-related protein increases feeding (Dicentrarchus labrax): dependence on the reproductive status and interaction with and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo. Endo- NPY and GnRH. Gen. Comp. Endocrinol. 132, 284–292. crinology 139, 4428–4431. Pfaffmann, C., Norgren, R., Grill, H.J., 1977. Sensory affect and motivation. Ann. N. Y. Acad. Rousseau, K., Dufour, S., 2007. Comparative aspects of GH and metabolic regulation in Sci. 290, 18–34. lower vertebrates. Neuroendocrinology 86, 165–174. Piekarski, D.J., Zhao, S., Jennings, K.J., Iwasa, T., Kriegsfeld, L.J., 2012. Gonadotropin-inhibitory Rowland, N., 1982. Failure by deprived hamsters to increase food intake: some behavioral hormone reduces sexual motivation and paracopulatory behaviors but not copulatory and physiological determinants. J. Comp. Physiol. Psychol. 96, 591–603. behavior in female Syrian hamsters, Society for Behavioral Neuroendocrinology. Horm. Roy, E.J., Wade, G.N., 1977. Role of food intake in estradiol-induced body weight changes Behav. (Madison, Wisconsin). in female rats. Horm. Behav. 8, 265–274. Pierce, A.A., Ferkin, M.H., 2005. Re-feeding and the restoration of odor attractivity, odor Sachs, B.D., 1965. Sexual behavior of male rats after one to nine days without food. preference, and sexual receptivity in food-deprived female meadow voles. Physiol. J. Comp. Physiol. Psychol. 60, 144–146. Behav. 84, 553–561. Sahu, A., Crowley, W.R., Tatemoto, K., Balasubramaniam, A., Kalra, S.P., 1987. Effects of Pierce, A.A., Ferkin, M.H., Williams, T.K., 2005. Food-deprivation-induced changes in neuropeptide Y, NPY analog (norleucine4-NPY), galanin and neuropeptide K on LH sexual behavior of meadow voles, Microtus pennsylvanicus. Anim. Behav. 70, release in ovariectomized (ovx) and ovx estrogen, progesterone-treated rats. Peptides 339–348. 8, 921–926. Pierce, A.A., Iwueke, I., Ferkin, M.H., 2007. Food deprivation and the role of estradiol in Sajapitak, S., Iwata, K., Shahab, M., Uenoyama, Y., Yamada, S., Kinoshita, M., Bari, F.Y., mediating sexual behaviors in meadow voles. Physiol. Behav. 90, 353–361. I'Anson, H., Tsukamura, H., Maeda, K., 2008. Central lipoprivation-induced suppres- Powers, J.B., 1970. Hormonal control of sexual receptivity during the estrous cycle of the sion of luteinizing hormone pulses is mediated by paraventricular catecholaminergic rat. Physiol. Behav. 5, 831–835. inputs in female rats. Endocrinology 149, 3016–3024. Powley, T.L., 2000. Vagal circuitry mediating cephalic-phase responses to food. Appetite Sakurai, H., Kawashima, M., Kamiyoshi, M., Tanaka, K., 1986. Effect of serotonin and beta- 34, 184–188. endorphin on the release of luteinizing hormone in the hen (Gallus domesticus). Gen. Presse, F., Sorokovsky, I., Max, J.P., Nicolaidis, S., Nahon, J.L., 1996. Melanin-concentrating Comp. Endocrinol. 63, 24–30. hormone is a potent anorectic peptide regulated by food-deprivation and glucopenia Sakurai, T., Amemiya, A., Ishii, M., Matsuzaki, I., Chemelli, R.M., Tanaka, H., William, S.C., in the rat. Neuroscience 71, 735–745. Richardson, J.A., Kozlowski, G.P., Wilson, S., Arch, J.R.S., Buckingham, R.E., Haynes, Pu, S., Jain, M.R., Kalra, P.S., Kalra, S.P., 1998. Orexins, a novel family of hypothalamic A.C., Carr, S.A., Annan, R.S., McNulty, D.E., Liu, W.S., Terrett, J.A., Elshourbagy, N.A., neuropeptides, modulate pituitary luteinizing hormone secretion in an ovarian Bergsma, D.J., Yanagisawa, M., 1998. Orexins and orexin receptors: a family of steroid-dependent manner. Regul. Pept. 78, 133–136. hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding Putnam, C.D., Brann, D.W., Mahesh, V.B., 1991. Acute activation of the adrenocorticotropin- behavior. Cell 92, 573–585. adrenal axis: effect on gonadotropin and prolactin secretion in the female rat. Endocri- Salamone, J.D., Correa, M., Farrar, A.M., Nunes, E.J., Pardo, M., 2009. Dopamine, behavioral nology 128, 2558–2566. economics, and effort. Front. Behav. Neurosci. 3, 13. Putti, R., Varricchio, E., Gay, F., Elena, C., Paolucci, M., 2009. Leptin effects on testis and Salazar,V.,Stoddard,P.,2009.Social competition affects electric signal plasticity and steroid epididymis in the lizard Podarcis sicula, during summer regression. Gen. Comp. levels in the gymnotiform fish (Brachyhypopomus gauderio).Horm.Behav.56,399–409. Endocrinol. 160, 168–175. Satake, H., Hisada, M., Kawada, T., Minakata, H., Ukena, K., Tsutsui, K., 2001. Characteriza- Qi, Y., Takahashi, N., Hileman, S.M., Patel, H.R., Berg, A.H., Pajvani, U.B., Scherer, P.E., tion of a cDNA encoding a novel avian hypothalamic neuropeptide exerting an inhib- Ahima, R.S., 2004. Adiponectin acts in the brain to decrease body weight. Nat. Med. itory effect on gonadotropin release. Biochem. J. 354, 379–385. 10, 524–529. Savory, C.J., Hodgkiss, J.P., 1984. Influence of vagotomy in domestic fowls on feeding activ- Qian, M., Wu, G.S., Adem, A., Johnson, A.E., Sodersten, P., 1999. CCK-8 can inhibit ingestive ity, food passage, digestibility and satiety effects of two peptides. Physiol. Behav. 33, behavior by acting on the liver. Neuroreport 10, 359–362. 937–944. J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728 727

Scheuerlein, A., Gwinner, E., 2002. Is food availability a circannual zeitgeber in tropical birds? Sirinathsinghji, D.J., Whittington, P.E., Audsley, A., Fraser, H.M., 1983. beta-Endorphin A field experiment on stonechats in tropical Africa. J. Biol. Rhythms 17, 171–180. regulates lordosis in female rats by modulating LH-RH release. Nature 301, 62–64. Schioth, H.B., Kakizaki, Y., Kohsaka, A., Suda, T., Watanobe, H., 2001. Agouti-related pep- Sisk, C.L., Bronson, F.H., 1986. Effects of food restriction and restoration on gonadotropin tide prevents steroid-induced luteinizing hormone and prolactin surges in female and growth hormone secretion in immature male rats. Biol. Reprod. 35, 554–561. rats. Neuroreport 12, 687–690. Smith, W.I., Ross, S., 1950. Hoarding behavior in the golden hamster (Mesocricetus auratus Schjolden, J., Schioth, H.B., Larhammar, D., Winberg, S., Larson, E.T., 2009. Melanocortin auratus). J. Genet. Psychol. 77, 211–215. peptides affect the motivation to feed in rainbow trout (Oncorhynchus mykiss). Gen. Smith, J.T., Coolen, L.M., Kriegsfeld, L.J., Sari, I.P., Jaafarzadehshirazi, M.R., Maltby, M., Comp. Endocrinol. 160, 134–138. Bateman, K., Goodman, R.L., Tilbrook, A.J., Ubuka, T., Bentley, G.E., Clarke, I.J., Schneider, J.E., 2004. Energy balance and reproduction. Physiol. Behav. 81, 289–317. Lehman, M.N., 2008. Variation in kisspeptin and RFamide-related peptide (RFRP) ex- Schneider, J.E., 2006. Metabolic and hormonal control of the desire for food and sex: pression and terminal connections to gonadotropin-releasing hormone neurons in implications for obesity and eating disorders. Horm. Behav. 50, 562–571. the brain: a novel medium for seasonal breeding in the sheep. Endocrinology 149, Schneider, J.E., Wade, G.N., 1989. Availability of metabolic fuels controls estrous cyclicity 5770–5782. of Syrian hamsters. Science 244, 1326–1328. Spina, M., Merlo-Pich, E., Chan, R.K., Basso, A.M., Rivier, J., Vale, W., Koob, G.F., 1996. Schneider, J.E., Watts, A.G., 2002. Energy balance, ingestive behavior and reproductive Appetite-suppressing effects of urocortin, a CRF-related neuropeptide. Science 273, success. In: Pfaff, D.W., Etgen, A., Fahrbach, S.F., Rubin, R.T. (Eds.), Hormones, Brain 1561–1564. and Behavior. Elsevier, San Diego, California, pp. 435–523. Stanley, B.G., Leibowitz, S.F., 1984. Neuropeptide Y: stimulation of feeding and drinking by Schneider, J.E., Watts, A.G., 2009. Energy Partitioning, Ingestive Behavior and Reproductive injection into the paraventricular nucleus. Life Sci. 35, 2635–2642. Success. In: Pfaff, D.W., Arnold, A.P., Etgen, A.M., Fahrbach, S.E., Rubin, R.T. (Eds.), Stanley, S.A., Small, C.J., Kim, M.S., Heath, M.M., Seal, L.J., Russell, S.H., Ghatei, M.A., Bloom, Hormones, Brain and Behavior. Elsevier, Oxford, UK. S.R., 1999. Agouti related peptide (Agrp) stimulates the hypothalamo pituitary Schneider, J.E., Lazzarini, S.J., Friedman, M.I., Wade, G.N., 1988. Role of fatty acid oxidation gonadal axis in vivo & in vitro in male rats. Endocrinology 140, 5459–5462. in food intake and hunger motivation in Syrian hamsters. Physiol. Behav. 43, 617–623. Stark, K.L., 1998. Agrp, a novel gene implicated in the control of feeding. Expert Opin. Schneider, J.E., Goldman, M.D., Tang, S., Bean, B., 1997. Leptin, metabolic fuels and repro- Investig. Drugs 7, 859–864. duction in Syrian hamsters. Soc. Neurosci. Abstr. 23, 417. Steiner, J.E., Glaser, D., Hawilo, M.E., Berridge, K.C., 2001. Comparative expression of Schneider, J.E., Goldman, M.D., Tang, S., Bean, B., Ji, H., Friedman, M.I., 1998. Leptin indirectly hedonic impact: affective reactions to taste by human infants and other primates. affects estrous cycles by increasing metabolic fuel oxidation. Horm. Behav. 33, 217–228. Neurosci. Biobehav. Rev. 25, 53–74. Schneider, J.E., Blum, R.M., Wade, G.N., 2000. Metabolic control of food intake and estrous Stengel, A., Wang, L., Goebel-Stengel, M., Tache, Y., 2011. Centrally injected kisspeptin cycles in Syrian hamsters. I. Plasma insulin and leptin. Am. J. Physiol. Regul. Integr. reduces food intake by increasing meal intervals in mice. Neuroreport 22, 253–257. Comp. Physiol. 278, R476–R485. Stevenson, J.A., Franklin, C., 1970. Effects of ACTH and corticosteroids in the regulation of Schneider,J.E.,Casper,J.F.,Barisich,A.,Schoengold,C.,Cherry,S.,Surico,J.,DeBarba,A.,Fabris, food and water intake. Prog. Brain Res. 32, 141–152. F., Rabold, E., 2007. Food deprivation and leptin prioritize ingestive and sex behavior Steward, C.A., Horan, T.L., Schuhler, S., Bennett, G.W., Ebling, F.J., 2003. Central administra- without affecting estrous cycles in Syrian hamsters. Horm. Behav. 51, 413–427. tion of thyrotropin releasing hormone (TRH) and related peptides inhibits feeding Schneider, J.E., Klingerman, C.M., Abdulhay, A., 2012. Sense and nonsense in metabolic control behavior in the Siberian hamster. Neuroreport 14, 687–691. of reproduction. Front. Endocrinol. 3, 26. http://dx.doi.org/10.3389/fendo.2012.00026. Strader, A.D., Buntin, J.D., 2001. Neuropeptide-Y: a possible mediator of prolactin-induced Schwartz, M.W., Porte Jr., D., 2005. Diabetes, obesity, and the brain. Science 307, 375–379. feeding and regulator of energy balance in the ring dove (Streptopelia risoria). Schwartz, M.W., Baskin, D.G., Bukowski, T.R., Kuijper, J.L., Foster, D., Lasser, G., Prunkard, J. Neuroendocrinol. 13, 386–392. D.E., Porte Jr., D., Woods, S.C., Seeley, R.J., Weigle, D.S., 1996. Specificity of leptin action Strader, A.D., Schioth, H.B., Buntin, J.D., 2003. The role of the melanocortin system and the on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression melanocortin-4 receptor in ring dove (Streptopelia risoria) feeding behavior. Brain in ob/ob mice. Diabetes 45, 531–535. Res. 960, 112–121. Schwartz, M.W., Woods, S.C., Porte Jr., D., Seeley, R.J., Baskin, D.G., 2000. Central nervous Szymanski, L.A., Schneider, J.E., Friedman, M.I., Ji, H., Kurose, Y., Blache, D., Rao, A., system control of food intake. Nature 404, 661–671. Dunshea, F.R., Clarke, I.J., 2007. Changes in insulin, glucose and ketone bodies, but Sederholm, F., Ammar, A.A., Sodersten, P., 2002. Intake inhibition by NPY: role of appeti- not leptin or body fat content precede restoration of luteinising hormone secretion tive ingestive behavior and aversion. Physiol. Behav. 75, 567–575. in ewes. J. Neuroendocrinol. 19, 449–460. Seeley, R.J., Payne, C.J., Woods, S.C., 1995. Neuropeptide Y fails to increase intraoral intake Szymanski, L.A., Schneider, J.E., Satragno, A., Dunshea, F.R., Clarke, I.J., 2011. Mesenteric in rats. Am. J. Physiol. 268, R423–R427. infusion of a volatile fatty acid prevents body weight loss and transiently restores Segal-Lieberman, G., Trombly, D.J., Juthani, V., Wang, X., Maratos-Flier, E., 2003. NPY abla- luteinising hormone pulse frequency in ovariectomised, food-restricted ewes. tion in C57BL/6 mice leads to mild obesity and to an impaired refeeding response to J. Neuroendocrinol. 23, 699–710. fasting. Am. J. Physiol. Endocrinol. Metab. 284, E1131–E1139. Tachibana, T., Takagi, T., Tomonaga, S., Ohgushi, A., Ando, R., Denbow, D.M., Furuse, M., Seymour, P.L., Dettloff, S.L., Jones, J.E., Wade, G.N., 2005. Corticotropin-releasing factor 2003. Central administration of cocaine- and amphetamine-regulated transcript receptor subtypes mediating nutritional suppression of estrous behavior in Syrian inhibits food intake in chicks. Neurosci. Lett. 337, 131–134. hamsters. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289, R418–R423. Tachibana, T., Sato, M., Takahashi, H., Ukena, K., Tsutsui, K., Furuse, M., 2005. Gonadotropin- Shah, S.N., Nyby, J.G., 2010. Ghrelin's quick inhibition of androgen-dependent behaviors inhibiting hormone stimulates feeding behavior in chicks. Brain Res. 1050, 94–100. of male house mice (Mus musculus). Horm. Behav. 57, 291–296. Tachibana, T., Sato, M., Oikawa, D., Furuse, M., 2006. Involvement of CRF on the anorexic Shahab, M., Sajapitak, S., Tsukamura, H., Kinoshita, M., Matsuyama, S., Ohkura, S., Yamada, effect of GLP-1 in layer chicks. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 143, S., Uenoyama, Y., I'Anson, H., Maeda, K., 2006. Acute lipoprivation suppresses pulsa- 112–117. tile luteinizing hormone secretion without affecting food intake in female rats. Tachibana, T., Oikawa, D., Takahashi, H., Boswell, T., Furuse, M., 2007. The anorexic effect of J. Reprod. Dev. 52, 763–772. alpha-melanocyte-stimulating hormone is mediated by corticotrophin-releasing fac- Shanbhag, B.A., Prasad, B.S., 1992. Fat body ovarian relationship in the garden lizard, tor in chicks. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 147, 173–178. Calotes versicolor (Daud.). J. Exp. Zool. 264, 454–460. Tachibana,T.,Matsuda,K.,Sawa,H.,Mikami,A.,Ueda,H.,Cline,M.A.,2010.Differen- Sharp, P.J., Dunn, I.C., Waddington, D., Boswell, T., 2008. Chicken leptin. Gen. Comp. tial thresholds of neuromedins B-, C-, and bombesin-induced anorexia and crop- Endocrinol. 158, 2–4. emptying rate in chicks. Gen. Comp. Endocrinol. 169, 144–150. Shelton, R.C., Miller, A.H., 2010. Eating ourselves to death (and despair): the contribution Tachibana, T., Matsuda, K., Kawamura, M., Ueda, H., Khan, M.S., Cline, M.A., 2012. Feeding- of adiposity and inflammation to depression. Prog. Neurobiol. 91, 275–299. suppressive mechanism of sulfated cholecystokinin (26–33) in chicks. Comp. Sherrington, C.S., 1906. The Integrative Action of the Nervous System. Scribner, New York. Biochem. Physiol. A Mol. Integr. Physiol. 161, 372–378. Sherry, D.F., Mrosovsky, N., Hogan, J.A., 1980. Weight loss and anorexia during incubation Takahashi, L.K., Lisk, R.D., Burnett 2nd, A.L., 1985. Dual estradiol action in diencephalon in birds. J. Comp. Physiol. Psychol. 94, 89–98. and the regulation of sociosexual behavior in female golden hamsters. Brain Res. Shimakura, S., Miura, T., Maruyama, K., Nakamachi, T., Uchiyama, M., Kageyama, H., 359, 194–207. Shioda, S., Takahashi, A., Matsuda, K., 2008. Alpha-melanocyte-stimulating hormone Tarin, J.J., Gomez-Piquer, V., 2002. Do women have a hidden heat period? Hum. Reprod. mediates melanin-concentrating hormone-induced anorexigenic action in goldfish. 17, 2243–2248. Horm. Behav. 53, 323–328. Te Marvelde, L., Visser, M.E., 2012. Manipulation of life-history decisions using leptin in a Shimizu, H., Shargill, N.S., Bray, G.A., Yen, T.T., Gesellchen, P.D., 1989. Effects of MSH on food wild passerine. PLoS One 7, e34090. intake, body weight and coat color of the yellow obese mouse. Life Sci. 45, 543–552. Temple, J.L., Millar, R.P., Rissman, E.F., 2003. An evolutionarily conserved form of Shine, R., 2003. Reproductive strategies in snakes. Proc. Biol. Sci. 270, 995–1004. gonadotropin-releasing hormone coordinates energy and reproductive behavior. Shine, R., Olsson, M.M., Moore, I.T., Lemaster, M.P., Greene, M., Mason, R.T., 2000. Body Endocrinology 144, 13–19. size enhances mating success in male garter snakes. Anim. Behav. 59, F4–F11. Tena-Sempere, M., Felip, A., Gomez, A., Zanuy, S., Carrillo, M., 2012. Comparative insights Sibly, R.M., Witt, C.C., Wright, N.A., Venditti, C., Jetz, W., Brown, J.H., 2012. Energetics, of the kisspeptin/kisspeptin receptor system: lessons from non-mammalian verte- lifestyle, and reproduction in birds. Proc. Natl. Acad. Sci. U.S.A. 109, 10937–10941. brates. Gen. Comp. Endocrinol. 175, 234–243. Siegel, L.I., Nunez, A.A., Wade, G.N., 1981. Effects of androgens on dietary self-selection Teubner, B.J., Bartness, T.J., 2010. Cholecystokinin-33 acutely attenuates food foraging, and carcass composition in male rats. J. Comp. Physiol. Psychol. 95, 529–539. hoarding and intake in Siberian hamsters. Peptides 31, 618–624. Silverman, H.J., Zucker, I., 1976. Absence of post-fast food compensation in the golden Teubner, B.J., Keen-Rhinehart, E., Bartness, T.J., 2012. Third ventricular coinjection of hamster (Mesocricetus auratus). Physiol. Behav. 17, 271–285. subthreshold doses of NPY and AgRP stimulate food hoarding and intake and neural Silverstein, J.T., Bondareva, V.M., Leonard, J.B., Plisetskaya, E.M., 2001. Neuropeptide regu- activation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 302, R37–R48. lation of feeding in catfish, Ictalurus punctatus: a role for glucagon-like peptide-1 Thody, A.J., Wilson, C.A., Everard, D., 1981. alpha-Melanocyte stimulating hormone stim- (GLP-1)? Comp. Biochem. Physiol. B Biochem. Mol. Biol. 129, 623–631. ulates sexual behaviour in the female rat. Psychopharmacology 74, 153–156. Sipos, M.L., Nyby, J.G., 1998. Intracranial androgenic activation of male-typical behaviours Thomas, D.W., Blondel, J., Perret, P., Lambrechts, M.M., Speakman, J.R., 2001. Energetic and in house mice: concurrent stimulation of the medial preoptic area and medial nucle- fitness costs of mismatching resource supply and demand in seasonally breeding us of the amygdala. J. Neuroendocrinol. 10, 577–586. birds. Science 291, 2598–2600. 728 J.E. Schneider et al. / Hormones and Behavior 64 (2013) 702–728

Tiefer, L., Johnson, W.A., 1971. Female sexual behaviour in male golden hamsters. Wade, G.N., Gray, J.M., Bartness, T.J., 1985. Gonadal influences on adiposity. Int. J. Obes. 9 J. Endocrinol. 51, 615–620. (Suppl. 1), 83–92. Tobiansky, D.J., Roma, P.G., Hattori, T., Will, R.G., Nutsch, V.L., Dominguez, J.M., 2013. The Wade, G.N., Schneider, J.E., Friedman, M.I., 1991. Insulin-induced anestrus in Syrian medial preoptic area modulates cocaine-induced activity in female rats. Behav. hamsters. Am. J. Physiol. 260, R148–R152. Neurosci. 127, 293–302. Wade, G.N., Lempicki, R.L., Panicker, A.K., Frisbee, R.M., Blaustein, J.D., 1997. Leptin facilitates Todd, B.J., Fraley, G.S., Peck, A.C., Schwartz, G.J., Etgen, A.M., 2007. Central insulin-like and inhibits sexual behavior in female hamsters. Am. J. Physiol. 272, R1354–R1358. growth factor 1 receptors play distinct roles in the control of reproduction, food Waldbillig, R.J., 1975. Attack, eating, drinking, and gnawing elicited by electrical stimula- intake, and body weight in female rats. Biol. Reprod. 77, 492–503. tion of rat mesencephalon and pons. J. Comp. Physiol. Psychol. 89, 200–212. Todd,B.J.,Merhi,Z.O.,Shu,J.,Etgen,A.M.,Neal-Perry,G.S.,2010.Hypothalamic Wallen, K., 2001. Sex and context: hormones and primate sexual motivation. Horm. insulin-like growth factor-I receptors are necessary for hormone-dependent Behav. 40, 339–357. luteinizing hormone surges: implications for female reproductive aging. Endocri- Wang, T., Hung, C.C., Randall, D.J., 2006. The comparative physiology of food deprivation: nology 151, 1356–1366. from feast to famine. Annu. Rev. Physiol. 68, 223–251. Torii, M., Kubo, K., Sasaki, T., 1999. Facilitatory and inhibitory effects of beta-endorphin on Wang, O., Sakihara, S., Gudmundsson, K., Majzoub, J., 2012. Leptin is Not Required for lordosis in female rats: relation to time of administration. Horm. Behav. 35, 271–278. Fertility. Endocrine Society, Houston, Texas. Tovar, S., Nogueiras, R., Tung, L.Y., Castaneda, T.R., Vazquez, M.J., Morris, A., Williams, L.M., Warham, J., 1996. The Behaviour, Population Biology and Physiology of Petrels. Academic Dickson, S.L., Dieguez, C., 2005. Central administration of resistin promotes short- Press, London. term satiety in rats. Eur. J. Endocrinol. 153, R1–R5. Watanobe, H., Schioth, H.B., Wikberg, J.E., Suda, T., 1999. The melanocortin 4 receptor Travers, S.P., Hu, H., 2000. Extranuclear projections of rNST neurons expressing gustatory- mediates leptin stimulation of luteinizing hormone and prolactin surges in steroid- elicited Fos. J. Comp. Neurol. 427, 124–138. primed ovariectomized rats. Biochem. Biophys. Res. Commun. 257, 860–864. Travers, S.P., Travers, J.B., 2007. Taste-evoked Fos expression in nitrergic neurons in the Watts, H.E., Hahn, T.P., 2012. Non-photoperiodic regulation of reproductive physiology in nucleus of the solitary tract and reticular formation of the rat. J. Comp. Neurol. 500, the flexibly breeding pine siskin (Spinus pinus). Gen. Comp. Endocrinol. 178, 259–264. 746–760. Whitman, D.C., Albers, H.E., 1995. Role of oxytocin in the hypothalamic regulation of Travers, J.B., Herman, K., Travers, S.P., 2010. Suppression of third ventricular NPY-elicited sexual receptivity in hamsters. Brain Res. 680, 73–79. feeding following medullary reticular formation infusions of muscimol. Behav. Wigby, S., Slack, C., Gronke, S., Martinez, P., Calboli, F.C., Chapman, T., Partridge, L., Neurosci. 124, 225–233. 2011. Insulin signalling regulates remating in female Drosophila. Proc. Biol. Sci. Trivers, R.L., 1972. Parental investment and sexual selection. In: Campbell, B.C. (Ed.), 278, 424–431. Sexual Selection and the Descent of Man. Aldine, Chicago. Williams, K.W., Margatho, L.O., Lee, C.E., Choi, M., Lee, S., Scott, M.M., Elias, C.F., Elmquist, True, C., Kirigiti, M.A., Kievit, P., Grove, K.L., Smith, M.S., 2011. Leptin is not the Critical Sig- J.K., 2010. Segregation of acute leptin and insulin effects in distinct populations of nal for Kisspeptin or Luteinising Hormone Restoration During Exit from Negative En- arcuate proopiomelanocortin neurons. J. Neurosci. Off. J. Soc. Neurosci. 30, 2472–2479. ergy Balance. Journal of Neuroendocrinology 23, 1099–1112. Wingfield, J.C., 2008. Comparative endocrinology, environment and global change. Gen. Tschop, M., Smiley, D.L., Heiman, M.L., 2000. Ghrelin induces adiposity in rodents. Nature Comp. Endocrinol. 157, 207–216. 407, 908–913. Wise, R.A., 2004. Dopamine and food reward: back to the elements. Am. J. Physiol. Regul. Tsukamura, H., Thompson, R.C., Tsukahara, S., Ohkura, S., Maekawa, F., Moriyama, R., Integr. Comp. Physiol. 286, R13. Niwa, Y., Foster, D.L., Maeda, K., 2000a. Intracerebroventricular administration of Witt, D.M., Young, L.J., Crews, D., 1995. Progesterone modulation of androgen-dependent melanin-concentrating hormone suppresses pulsatile luteinizing hormone release sexual behavior in male rats. Physiol. Behav. 57, 307–313. in the female rat. J. Neuroendocrinol. 12, 529–534. Wood, A.D., Bartness, T.J., 1996. Caloric density affects food hoarding and intake by Tsukamura, H., Tsukahara, S., Maekawa, F., Moriyama, R., Reyes, B.A., Sakai, T., Niwa, Y., Siberian hamsters. Physiol. Behav. 59, 897–903. Foster, D.L., 2000b. Peripheral or central administration of motilin suppresses LH Wood, A.D., Bartness, T.J., 1997. Partial lipectomy, but not PVN lesions, increases food release in female rats: a novel role for motilin. J. Neuroendocrinol. 12, 403–408. hoarding by Siberian hamsters. Am. J. Physiol. 272, R783–R792. Turton, M.D., O'Shea, D., Gunn, I., Beak, S.A., Edwards, C.M., Meeran, K., Choi, S.J., Taylor, Woods, S.C., Lotter, E.C., McKay, L.D., Porte Jr., D., 1979. Chronic intracerebroventricular G.M., Heath, M.M., Lambert, P.D., Wilding, J.P., Smith, D.M., Ghatei, M.A., Herbert, J., infusion of insulin reduces food intake and body weight of baboons. Nature 282, Bloom, S.R., 1996. A role for glucagon-like peptide-1 in the central regulation of 503–505. feeding. Nature 379, 69–72. Woods, S.C., Seeley, R.J., Cota, D., 2008. Regulation of food intake through hypothalamic Uenoyama, Y., Tsukamura, H., Kinoshita, M., Yamada, S., Iwata, K., Pheng, V., Sajapitak, S., signaling networks involving mTOR. Annu. Rev. Nutr. 28, 295–311. Sakakibara, M., Ohtaki, T., Matsumoto, H., Maeda, K.I., 2008. Oestrogen-dependent Wren, A.M., Small, C.J., Ward, H.L., Murphy, K.G., Dakin, C.L., Taheri, S., Kennedy, A.R., stimulation of luteinising hormone release by galanin-like peptide in female rats. Roberts, G.H., Morgan, D.G., Ghatei, M.A., Bloom, S.R., 2000. The novel hypothalamic J. Neuroendocrinol. 20, 626–631. peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology Ur, E., Grossman, A., Despres, J.P., 1996. Obesity results as a consequence of glucocorticoid 141, 4325–4328. induced leptin resistance. Horm. Metab. Res. 28, 744–747. Wu, Q., Boyle, M.P., Palmiter, R.D., 2009. Loss of GABAergic signaling by AgRP neurons to Van Der Kolk, N., Madison, F.N., Mohr, M., Eberhard, N., Kofler, B., Fraley, G.S., 2010. Alarin the parabrachial nucleus leads to starvation. Cell 137, 1225–1234. stimulates food intake in male rats and LH secretion in castrated male rats. Neuro- Wu, Q., Whiddon, B.B., Palmiter, R.D., 2012. Ablation of neurons expressing agouti-related peptides 44, 333–340. protein, but not melanin concentrating hormone, in leptin-deficient mice restores Van Dyke, J.U., Beaupre, S.J., 2011. Bioenergetic components of reproductive effort in metabolic functions and fertility. Proc. Natl. Acad. Sci. U.S.A. 109, 3155–3160. viviparous snakes: costs of vitellogenesis exceed costs of pregnancy. Comp. Biochem. Xu, Y., Nedungadi, T.P., Zhu, L., Sobhani, N., Irani, B.G., Davis, K.E., Zhang, X., Zou, F., Gent, Physiol. A Mol. Integr. Physiol. 160, 504–515. L.M., Hahner, L.D., Khan, S.A., Elias, C.F., Elmquist, J.K., Clegg, D.J., 2011. Distinct hypo- Vander Wall, S.B., 1990. Food Hoarding in Animals. University of Chicago Press, Chicago thalamic neurons mediate estrogenic effects on energy homeostasis and reproduc- (London). tion. Cell Metab. 14, 453–465. Vaughan, C.H., Shrestha, Y.B., Bartness, T.J., 2011. Characterization of a novel melanocortin Yanagita, K., Shiraishi, J., Fujita, M., Bungo, T., 2008. Effects of N-terminal fragments of receptor-containing node in the SNS outflow circuitry to brown adipose tissue beta-endorphin on feeding in chicks. Neurosci. Lett. 442, 140–142. involved in thermogenesis. Brain Res. 1411, 17–27. Yang, H.D., Wang, Q., Wang, Z., Wang, D.H., 2011. Food hoarding and associated neuronal acti- Vergoni, A.V., Poggioli, R., Bertolini, A., 1986. Corticotropin inhibits food intake in rats. vation in brain reward circuitry in Mongolian gerbils. Physiol. Behav. 104, 429–436. Neuropeptides 7, 153–158. Yu, J.Y., Dickhoff, W.W., Swanson, P., Gorbman, A., 1981. Vitellogenesis and its hormonal reg- Vetter, M.L., Faulconbridge, L.F., Webb, V.L., Wadden, T.A., 2010. Behavioral and pharma- ulationinthepacifichagfish, Eptatretus stouti L. Gen. Comp. Endocrinol. 43, 492–502. cologic therapies for obesity. Nat. Rev. Endocrinol. 6, 578–588. Zemel, M.B., Shi, H., 2000. Pro-opiomelanocortin (POMC) deficiency and peripheral Vijayan, E., McCann, S.M., 1977. Suppression of feeding and drinking activity in rats melanocortins in obesity. Nutr. Rev. 58, 177–180. following intraventricular injection of thyrotropin releasing hormone (TRH). Endo- Zhang,C.,Bosch,M.A.,Ronnekleiv,O.K.,Kelly,M.J.,2009.Gamma-aminobutyric acid B crinology 100, 1727–1730. receptor mediated inhibition of gonadotropin-releasing hormone neurons is suppressed Volkoff, H., Bjorklund, J.M., Peter, R.E., 1999. Stimulation of feeding behavior and food con- by kisspeptin-G protein-coupled receptor 54 signaling. Endocrinology 150, 2388–2394. sumption in the goldfish, Carassius auratus, by orexin-A and orexin-B. Brain Res. 846, Zhang, X.Y., Yang, H.D., Zhang, Q., Wang, Z., Wang, D.H., 2011. Increased feeding and food 204–209. hoarding following food deprivation are associated with activation of dopamine and Volkoff, H., Canosa, L.F., Unniappan, S., Cerda-Reverter, J.M., Bernier, N.J., Kelly, S.P., Peter, orexin neurons in male Brandt's voles. PLoS One 6, e26408. R.E., 2005. Neuropeptides and the control of food intake in fish. Gen. Comp. Zhang, C., Forlano, P.M., Cone, R.D., 2012. AgRPandPOMCneuronsarehypophysiotropicand Endocrinol. 142, 3–19. coordinately regulate multiple endocrine axes in a teleost. Cell Metab. 15, 256–264. Vreeburg, J.T., Samaun, K., Verkade, H.J., Verhoef, P., Ooms, M.P., Weber, R.F., 1988. Effects Zhao, Z.J., Cao, J., 2009. Plasticity in energy budget and behavior in Swiss mice and striped of corticosterone on the negative feedback action of testosterone, 5 alpha- hamsters under stochastic food deprivation and refeeding. Comp. Biochem. Physiol. A dihydrotestosterone and estradiol in the adult male rat. J. Steroid Biochem. 29, 93–98. Mol. Integr. Physiol. 154, 84–91. Wade, G.N., 1972. Gonadal hormones and behavioral regulation of body weight. Physiol. Zheng, H., Patterson, L.M., Rhodes, C.J., Louis, G.W., Skibicka, K.P., Grill, H.J., Myers Jr., M.G., Behav. 8, 523–534. Berthoud, H.R., 2010. A potential role for hypothalamomedullary POMC projections in Wade, G.N., Gray, J.M., 1979. Gonadal effects on food intake and adiposity: a metabolic leptin-induced suppression of food intake. Am. J. Physiol. Regul. Integr. Comp. Physiol. hypothesis. Physiol. Behav. 22, 583–593. 298, R720–R728. Wade, G.N., Jones, J.E., 2004. Neuroendocrinology of nutritional infertility. Am. J. Physiol. Zigman, J.M., Elmquist, J.K., 2003. Minireview: from anorexia to obesity—the yin and yang Regul. Integr. Comp. Physiol. 287, R1277–R1296. of body weight control. Endocrinology 144, 3749–3756. Wade, G.N., Schneider, J.E., 1992. Metabolic fuels and reproduction in female mammals. Zucker, I., 1969. Hormonal determinants of sex differences in saccharin preference, food Neurosci. Biobehav. Rev. 16, 235–272. intake and body weight. Physiol. Behav. 4, 595–602. Wade, G.N., Zucker, I., 1970. Modulation of food intake and locomotor activity in female Zucker, I., Wade, G.N., Ziegler, R., 1972. Sexual and hormonal influences on eating, taste rats by diencephalic hormone implants. J. Comp. Physiol. Psychol. 72, 328–336. preferences, and body weight of hamsters. Physiol. Behav. 8, 101–111.