title: Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole.
abstract: The central melanocortin (MC) system has been widely studied for its effects on food intake and sexual behavior. However, the MC system, and more specifically the MC4 receptor (MC4R), also interacts with neurochemical systems that regulate socioemotional behaviors, including oxytocin (OT) and dopamine. In monogamous prairie voles, OT and dopamine interact to promote partner preference formation, a laboratory measure of an enduring social bond between mates. Here we investigated the effects of MC receptor activation on partner preference formation in prairie voles, as well as the interaction between the MC and OT systems during this process. Peripheral administration of the brain penetrant MC3/4R receptor peptide agonist, Melanotan II (MTII), and the highly selective, small-molecule MC4R agonist, Pf-446687, enhanced partner preference formation in the prairie vole, but not in the non-monogamous meadow vole. MTII-induced partner preferences were enduring, as they were present 1 week after drug manipulation. The prosocial effects of MCR agonists may be mediated, in part, through modulation of OT, as coadministration of an OT receptor antagonist prevented MTII-induced partner preferences. MTII also selectively activated hypothalamic OT neurons and potentiated central OT release. As OT has been shown to enhance some aspects of social cognition in humans, our data suggest that the MC4R may be a viable therapeutic target for enhancing social function in psychiatric disorders, including autism spectrum disorders and schizophrenia, potentially through activation of the OT system.
authors: 1] Center Translational Social Neuroscience, Silvio O Conte Center for Oxytocin and Social Cognition, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA [2] Neuroscience Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA, USA.
authors: Meera E
authors: ME
authors: Modi
authors: Center Translational Social Neuroscience, Silvio O Conte Center for Oxytocin and Social Cognition, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors: Kiyoshi
authors: K
authors: Inoue
authors: Center Translational Social Neuroscience, Silvio O Conte Center for Oxytocin and Social Cognition, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors: Catherine E
authors: CE
authors: Barrett
authors: Center Translational Social Neuroscience, Silvio O Conte Center for Oxytocin and Social Cognition, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors: Kara A
authors: KA
authors: Kittelberger
authors: 1] Neuroscience Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA, USA [2] Autism Speaks, Boston, MA, USA.
authors: Daniel G
authors: 0000000346378992
authors: DG
authors: Smith
authors: Max Plank Institute of Psychiatry, Munich, Germany.
authors: Rainer
authors: R
authors: Landgraf
authors: Center Translational Social Neuroscience, Silvio O Conte Center for Oxytocin and Social Cognition, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors: Larry J
authors: LJ
authors: Young
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000378:metabolism; D003411:Arvicolinae; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D005260:Female; D008297:Male; D010121:Oxytocin / Q000378:metabolism* / Q000494:pharmacology; D010152:Pair Bond; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D044101:Receptors, Melanocortin / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C549342:1-((1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl)carbonyl)-3,5-dimethyl-4-phenylpiperidin-4-ol; D051766:Early Growth Response Protein 1; D010456:Peptides, Cyclic; D010880:Piperidines; D011759:Pyrrolidines; D044101:Receptors, Melanocortin; D018045:Receptors, Oxytocin; C112221:alpha-MSH (1-13)amide, (Nle(4),Phe(p-I)7)-; C096587:vasotocin, d(CH2)5-O--methyl-Tyr(2)-Thr(4)-N(delta)-propionyl-Orn(8)-Tyr(9)-NH2; D001127:Arginine Vasopressin; C079282:melanotan-II; D010121:Oxytocin; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; D014668:Vasotocin
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