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VIII. Peptide Hormones and Behavior: Cholecystokinin and Prolactin

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VIII. Peptide Hormones and Behavior: Cholecystokinin and Prolactin PeptideBrazilian hormones Journal of andMedical behavior and Biological Research (2001) 34: 1369-1377 1369 ISSN 0100-879X Virtual Symposium The brain decade in debate: VIII. Peptide hormones and behavior: cholecystokinin and prolactin M.C. Beinfeld1, 1Department of Pharmacology and Experimental Therapeutics, J.C. Bittencourt2, Tufts University School of Medicine, Boston, MA, USA R.S. Bridges3, 2Departamento de Anatomia, Instituto de Ciências Biomédicas, P.L. Faris4, Universidade de São Paulo, São Paulo, SP, Brasil A.B. Lucion5, 3Department of Biomedical Sciences, Tufts University School of A.G. Nasello6, Veterinary Medicine, North Grafton, MA, USA A. Weller7 and 4Division of Neuroscience Research, MMC 392, Department of Psychiatry, L.F. Felicio8 University of Minnesota, Medical School, Minneapolis, MN, USA 5Departamento de Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil 6Departamento de Ciências Fisiológicas, Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP, Brasil 7Developmental Psychobiology Laboratory, Department of Psychology, Bar Ilan University, Ramat, Gan, Israel 8Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP, Brasil Abstract Correspondence This article is a transcription of an electronic symposium held on Key words L.F. Felicio November 28, 2000 in which active researchers were invited by the · CCK Departamento de Patologia Brazilian Society of Neuroscience and Behavior (SBNeC) to discuss · PRL Faculdade de Medicina the advances of the last decade in the peptide field with particular · Dopamine Veterinária e Zootecnia, USP focus on central actions of prolactin and cholecystokinin. The com- · Maternal behavior Av. Orlando Marques Paiva, 87 · ments in this symposium reflect the diversity of prolactin and chole- Bulimia 05508-900 São Paulo, SP · Motivation Brasil cystokinin research and demonstrate how the field has matured. Since both peptides play a role in reproductive behaviors, particularly mother- The names of the authors are infant interactions, this was the starting point of the discussion. Recent presented in alphabetical order, findings on the role of the receptor subtypes as well as interaction with except for the last one that other peptides in this context were also discussed. Another issue corresponds to the symposium discussed was the possible role of these peptides in dopamine-medi- organizer. ated rewarding systems. Both prolactin and cholecystokinin are in- Publication supported by FAPESP. volved in mechanisms controlling food intake and somatic pain thresholds. The role of peripheral inputs through vagal afferents modulating behavior was stressed. The advent of knockout animals as potential generators of new knowledge in this field was also ad- Received August 8, 2001 dressed. Finally, interactions with other neuropeptides and investiga- Accepted August 27, 2001 tion of the role of these peptides in other fields such as immunology were mentioned. Knowledge about the central functions of prolactin and cholecystokinin has shown important advances. The role of these peptides in neurological and psychiatric syndromes such as anorexia, drug abuse and physiological disturbances that lead to a compromised maternal behavior seems relevant. Braz J Med Biol Res 34(11) 2001 1370 M.C. Beinfeld et al. Introduction medial preoptic area of steroid-primed vir- gin female rats stimulate a rapid onset of The versatility of peptide hormones is maternal behavior (1-5). I am interested in such that almost every peptide hormone is how we want to proceed with our discussion also a neuropeptide. It has been proposed of prolactin, cholecystokinin and behavior. that some of them may be neurotransmitters, Aron Weller: My relevant research fo- although, in general, they act as neuromodu- cuses on early, postnatal behavioral devel- lators. Actions of peptide hormones on the opment in the rat, and the role of cholecysto- central nervous system are almost always kinin in mediating various aspects: infant- related to their physiological functions at the mother interaction, stress and comfort, natu- periphery. Both peripheral and brain pep- ral and learned preferences, feeding, and tides are involved in behaviorally meaning- satiety. Dear Dr. Bridges, if I recall cor- ful nervous system functions. This is par- rectly, your research on cholecystokinin and ticularly true for cholecystokinin and prolac- maternal behavior found that it acts as an tin. These hormones induce satiety and fa- antagonist of opiate inhibition, and that it cilitate maternal behavior, respectively. Nev- affects maintenance, but not initiation of ertheless, a range of central cholecystokinin maternal behavior (6,7). These findings, re- and prolactin effects has been described re- ported in your studies with Felicio, are a few cently. Both cholecystokinin and prolactin years old. Is there an update? Is there a are involved in dopaminergic transmission. connection with prolactin? With humans? The interrelations of the cholecystokinin and Robert Bridges: Dr. Weller, we have not dopaminergic systems are responsible for pursued these studies to any extent over the the role of these peptides in several neuro- past few years. Rather, we have focused our logical and psychiatric syndromes such as efforts on the involvement of the prolactin Parkinson’s disease, Huntington’s chorea, receptor in regulating the onset of maternal schizophrenia, bulimia, anorexia and anxi- behavior. Our most recent efforts have dem- ety. Besides their interactions with the dopa- onstrated that central (medial preoptic area, minergic systems, there are important rela- MPOA) infusions of the prolactin receptor tions among prolactin, thyroid and gonadal antagonist, S179D-prolactin (5), delay the hormones since prolactin regulates the physi- onset of maternal care in steroid-primed nul- ological and pathological effects of these liparous rats. The interaction between pro- hormones. The relation between prolactin lactin and cholecystokinin certainly would and stress is well known. In addition, both be of interest to pursue. peptides have modulatory effects on each Aron Weller: Dr. Bridges and Dr. Felicio, other’s best-known central functions. in a manner analogous to your studies on initiation and maintenance of maternal be- From your results, which behavior(s) havior, Dr. Raymond Nowak of CNRS, is being affected by a particular Tours, France, has been studying the role of hormone? What is the systemic cholecystokinin receptors in the develop- mechanism of it? ment of preference for the mother (“bond- ing”) in sheep, and we have been studying Robert Bridges: My research focus that the role of cholecystokinin in infant-mother is relevant to this discussion pertains to the attraction/preference in rats (maintenance). role of prolactin and placental lactogens in We actually get a complicated pattern. Nowak the central regulation of maternal behavior (8) reports a blockade of bonding (prefer- in mammals. We have found that infusions ence toward the mother) by a CCK1 receptor of prolactin or rat placental lactogen into the antagonist, and a facilitation with a CCK2 Braz J Med Biol Res 34(11) 2001 Peptide hormones and behavior 1371 antagonist. We found increased preference interaction of neonatal stress and cholecys- rates toward aspects of the mother and nest tokinin on bonding and mother-infant inter- induced by antagonists of both receptor types action? (9,10). Dr. Felicio, Dr. Bridges said earlier Aron Weller: Dr. Lucion, regarding cen- that he hasn’t followed up your findings on tral cholecystokinin receptors: brain chole- cholecystokinin and maternal behavior. Do cystokinin receptors appear to have a prima- you have any recent (last few years) findings rily postnatal ontogeny. Studies of specific in that area? binding of cholecystokinin to rat forebrain Luciano Felicio: Both CCK1 and CCK2 and midbrain have shown an increase from (previously named CCKA and CCKB) (11) birth, peaking around days 12-13, staying receptor antagonists potentiate morphine in- high until about day 17-20, followed then by hibitory effects on ongoing maternal behav- a gradual decrease to adult levels in the ior. This is consistent with previous results fourth week of life. Simultaneously, the dis- that demonstrated antagonistic effects of tribution of brain cholecystokinin receptors cholecystokinin and beta-endorphin on this becomes gradually more extensive as the behavior. These results suggest that both pup matures: cholecystokinin receptors are subtypes of cholecystokinin receptors might first found in the central cingulate and pyri- be involved in this multiple peptidergic con- form cortices on postnatal day 1, confined to trol of maternal behavior in lactating rats limbic areas up to day 10, after which a rapid (12). In addition, we found that pretreatment development is noted, approximating the with the CCK1 antagonist lorglumide during adult’s distribution by day 15 (16-18). Re- late pregnancy disrupts maternal behavior in garding cholecystokinin, stress, bonding and rats (13). mother-infant interaction: an intriguing and Aldo Lucion: I have been studying the promising field! Not much is known, let’s role of oxytocin in maternal aggressive be- study it! havior. Dr. Weller, do you think cholecysto- Patricia Faris: Dr. Weller, I am very kinin would act directly on neurons or by interested in making some sense out of CCK1 means of stimulatory effects on oxytocin versus CCK2 antagonists. Our early
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