title: Neonatal melanocortin receptor agonist treatment reduces play fighting and promotes adult attachment in prairie voles in a sex-dependent manner.
abstract: The melanocortin receptor (MCR) system has been studied extensively for its role in feeding and sexual behavior, but effects on social behavior have received little attention. α-MSH interacts with neural systems involved in sociality, including oxytocin, dopamine, and opioid systems. Acute melanotan-II (MTII), an MC3/4R agonist, potentiates brain oxytocin (OT) release and facilitates OT-dependent partner preference formation in socially monogamous prairie voles. Here we examined the long-term impact of early-life MCR stimulation on hypothalamic neuronal activity and social development in prairie voles. Male and female voles were given daily subcutaneous injections of 10 mg/kg MTII or saline between postnatal days (PND) 1-7. Neonatally-treated males displayed a reduction in initiated play fighting bouts as juveniles compared to control males. Neonatal exposure to MTII facilitated partner preference formation in adult females, but not males, after a brief cohabitation with an opposite-sex partner. Acute MTII injection elicited a significant burst of the immediate early gene EGR-1 immunoreactivity in hypothalamic OT, vasopressin, and corticotrophin releasing factor neurons, when tested in PND 6-7 animals. Daily neonatal treatment with 1 mg/kg of a more selective, brain penetrant MC4R agonist, PF44687, promoted adult partner preferences in both females and males compared with vehicle controls. Thus, developmental exposure to MCR agonists lead to a persistent change in social behavior, suggestive of structural or functional changes in the neural circuits involved in the formation of social relationships.
authors.affiliation: Center for Translational Social Neuroscience, Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30329, USA. Electronic address: cbarrett27@gmail.com.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Barrett
authors.affiliation: Center for Translational Social Neuroscience, Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30329, USA.
authors.forename: Meera E
authors.initials: ME
authors.lastname: Modi
authors.affiliation: Center for Translational Social Neuroscience, Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30329, USA.
authors.forename: Billy C
authors.initials: BC
authors.lastname: Zhang
authors.affiliation: Center for Translational Social Neuroscience, Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30329, USA.
authors.forename: Hasse
authors.initials: H
authors.lastname: Walum
authors.affiliation: Center for Translational Social Neuroscience, Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30329, USA.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Center for Translational Social Neuroscience, Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30329, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Young
mesh_terms: D000374:Aggression / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D003411:Arvicolinae; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010152:Pair Bond; D010456:Peptides, Cyclic / Q000494:pharmacology; D010988:Play and Playthings; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011897:Random Allocation; D044104:Receptor, Melanocortin, Type 3 / Q000819:agonists* / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists* / Q000378:metabolism; D012727:Sex Characteristics; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D051766:Early Growth Response Protein 1; D010456:Peptides, Cyclic; D011619:Psychotropic Drugs; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; C079282:melanotan-II; D000521:alpha-MSH
keywords: Early experience; Melanocortin receptor; Melanotan-II; Oxytocin; Prairie voles; Social behavior