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Early Ventral Hippocampal Lesion Model Eating and Appetite

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Early Ventral Hippocampal Lesion Model Eating and Appetite E Early Ventral Hippocampal Lesion Definition Model Feeding reflects the behavioral response neces- Definition sary for replenishing energy substrates critical for survival, whereas appetite refers to the moti- An animal model in which the ventral hippocam- vational component of this behavior. pal region in rats is lesioned using an excitotoxic agent. This lesion is performed at an early age (typically postnatal day 7). These animals Impact of Psychoactive Drugs develop several schizophrenia-like phenomena in adulthood. Interestingly, most of the symptoms Feeding can be defined as the behavioral response occur after puberty in accordance with the clini- necessary for replenishing energy substrates to cal literature on schizophrenia. maintain energy balance and, ultimately, the sur- vival of all organisms. Predictably, a shortage of Cross-References food sources is associated with increased motiva- tional states that promote food seeking, as well ▶ Schizophrenia: Animal Models as metabolic changes that allow for energy stores ▶ Simulation Models to be amassed in the form of adipose tissue. In general, increases in these motivational states are commonly referred to as appetite (Berthoud Eating and Appetite and Morrison 2008). Feeding can also be elicited by the mere presence of food and, in the absence Alfonso Abizaid1 and Shimon Amir2 of a negative energy state, possibly as an adaptive 1Department of Neuroscience, Carleton behavioral response directed at storing excess University, Ottawa, ON, Canada energy in anticipation of future shortages. 2Department of Psychology, Center for Studies in Clearly, the mechanisms regulating feeding Behavioral Neurobiology, Concordia University, behavior are complex and involve both regula- Montreal, QC, Canada tory and nonregulatory processes. Peripheral signals regulating energy balance. Both food intake and appetite are influenced by Synonyms multiple neural and peripheral signals. These include energy substrates such as glucose, free Energy intake fatty acids, and amino acids; hormones such as # Springer-Verlag Berlin Heidelberg 2015 I.P. Stolerman, L.H. Price (eds.), Encyclopedia of Psychopharmacology, DOI 10.1007/978-3-642-36172-2 E 570 Eating and Appetite leptin, cholecystokinin (CCK), insulin, and than direct action on aminergic neurotransmitters. ghrelin; and neurotransmitters, including dopa- Rimonabant, a compound that blocks the cannabi- mine (DA), serotonin (5-HT), norepinephrine noid CB1 receptor, has some appetite suppressant (NE), and endocannabinoids. Moreover, drugs properties, although it has been recently rejected that affect these systems are currently used to as an antiobesity medication. Leptin, a hormone curb obesity and treat type II diabetes or to produced by white fat cells, also lowers food increase feeding in pathological conditions that intake and body weight and continues to be con- lead to anorexia and cachexia (e.g., cancer and sidered as a potential drug to treat obesity and chronic renal disease). Finally, drugs used to treat metabolic syndrome (Bray and Greenway 2007). other conditions have side effects that include Allofthesedrugshavebeenreportedtobeeffec- abnormal feeding behaviors (anorexia or overeat- tive in reducing appetite, but their effects are short- ing) (Berthoud and Morrison 2008). lived, possibly because of the development of tol- Pharmacological agents affecting feeding and erance (Fernstrom and Choi 2008). appetite. The complexity of neural mechanisms It is well known that typical (haloperidol) and underlying feeding behavior is reflected by the some atypical antipsychotic drugs (clozapine, number of pharmacological agents that are known olanzapine, and risperidone) increase appetite to affect this behavior. Commonly, these actions and body weight significantly. Conversely, are identified as side effects of treatments to other some atypical antipsychotic drugs, like pathological conditions and, subsequently, are used ziprasidone, may decrease appetite. Similarly, to control feeding behaviors. In some cases, these tricyclic antidepressants, monoamine oxidase medications are used to stimulate feeding in inhibitors, and some atypical antidepressants circumstances where patients are anorexic, but the also cause weight increases that range from mod- great majority of drugs aimed at modulating feed- erate to high (more than 10 %) over the treatment ing behavior are aimed at reducing caloric intake. It period. These medications include imipramine, is difficult, however, to identify a single neurotrans- phenelzine, mirtazapine, and trazodone. SSRIs mitter system as critical for food intake, as many are commonly associated with weight decreases have been implicated in the regulation of feeding early in treatment, but with body weight increases (Bray and Greenway 2007). after prolonged use. Treatment with the atypical Most appetite suppressants are drugs that antidepressant bupropion may result in decreased modify the release of monoamine and catechol- body weight (Jensen 2008). amine neurotransmitters in the brain. The most Central regulation of feeding and appetite. successful of these is sibutramine, a drug Feeding and appetite are both regulated by mul- approved by the US Food and Drug Administra- tiple brain regions (Berthoud and Morrison 2008; tion (FDA) for the treatment of obesity and Bray and Greenway 2007). The hypothalamus one that primarily inhibits the reuptake of 5-HT plays a predominant role in eliciting feeding and NE and, to a lesser extent, dopamine. responses as a means of achieving a homeostatic Sympathomimetics have also been approved by state. Early studies using hypothalamic lesions the FDA, including amphetamine, phentermine, emphasized the role of the mediobasal hypothal- benzphetamine, and phendimetrazine, although amus in mediating satiety responses and that of these are only prescribed for short-term use the lateral hypothalamus in mediating appetitive given their potential addictive properties. Finally, responses. More recently, however, it has become some antidepressant medications have anorectic clear that the hypothalamus contains a massive effects, including drugs such as fluoxetine, which peptidergic network that regulates food intake is a selective serotonin reuptake inhibitor (SSRI), and energy expenditure in response to hormonal and bupropion, a dopamine and norepinephrine and nutritional signals. One current idea is that reuptake inhibitor (Bray and Greenway 2007). the hypothalamic arcuate nucleus (ARC), There are a number of appetite suppressants a bilateral hypothalamic structure that surrounds that act through physiological mechanisms other the ventral portion of the third ventricle, plays Eating and Appetite 571 E a fundamental role in regulating feeding and signals from the mouth. Within the DVC, the energy homeostasis (Cone 2005). Indeed, the nucleus of the solitary tract (NTS) is the main ARC contains cells that are sensitive to all target for information ascending from the gut via peripheral signals that convey information about the vagus nerve and the enteric nervous system. energetic state and produce a number of peptides The NTS contains noradrenergic neurons that that influence food intake and appetite. A subset target and modulate the activity of hypothalamic of neurons in the ARC produce a-melanocyte- and limbic structures implicated in feeding, stimulating hormone (a-MSH), a cleaved product including the PVN and central nucleus of the of the proopiomelanocortin (POMC) precursor amygdala (CeA). The area postrema (AP), that decreases food intake and increases energy a second division of the DVC, lies outside of the E expenditure. A second subset of ARC neurons blood-brain barrier and is thus especially sensi- release two peptides that have a strong orexigenic tive to blood-borne nutritional signals, including effect: neuropeptide Y (NPY) and agouti-related those that are relayed by hormones like leptin, peptide (AGRP). Both a-MSH and AGRP com- insulin, cholecystokinin (CCK), and ghrelin, as pete for the same receptors (the melanocortin well as being sensitive to changes in circulating receptors 3 and 4, or MCR3 and MCR4) at target plasma levels of glucose. The AP transduces regions, with AGRP being a natural antagonist these signals and conveys them primarily to the and a-MSH being an agonist at these receptors NTS, where they are integrated with ascending (Cone 2005). Given these properties, the cells in visceral signals, but also directly onto the PVN, the ARC and the MCR3 and MCR4 receptors at where they may elicit feeding and autonomic their target brain sites are referred to as the responses. In addition to the regulation of feeding melanocortin system of energy regulation. In addi- responses, the brain stem plays a key role in the tion to NPY and melanocortin, peptides secreted generation of autonomic responses, being by other hypothalamic nuclei play an important involved in blood pressure regulation, respira- role in modulating feeding and appetite. For exam- tion, glucose release from the liver, vasoconstric- ple, cells in the lateral hypothalamus produce tion, lipolysis, and thermogenesis (Grill 2006). orexins/hypocretins or melanin-concentrating hor- Recent evidence has highlighted the role of the mone (MCH), both of which stimulate food intake midbrain in the regulation of feeding and appetite and appetitive responses. In contrast, cells in the (Volkow and Wise 2005). The midbrain contains paraventricular nucleus (PVN) of the hypothala- a number of cell groups implicated in brain func- mus release
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