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.

Severity of eating disorder symptoms related to oxytocin receptor polymorphisms in anorexia nervosa

“…In the context of the starvation, decreasing prosocial behavior in favor of feeding behaviors is appropriate, and consistent with animal studies (Barrett et al, 2014). Examination of the methylation status of risk genes in psychiatric illness may provide an additional indicator of gene expression (Hing et al, 2014).…”

Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism

“…Repeated OXT treatments during the first postnatal week increase the number of isolation-induced ultrasonic vocalizations (60), a measure of social vocal communication. In addition, daily neonatal treatment during this first week of life with a selective MC4R agonist promotes adult partner preference (61). Similarly, in mice, a single postnatal administration of OXT at P1 facilitated alloparental care and social approach in adulthood, while administration of an OXT antagonist produced the opposite effect (62) and sub-chronic OXT treatment in juvenile rats has long lasting effects in social behavior, which is accompanied by increased plasma OXT levels (63).…”

RNAi knockdown of oxytocin receptor in the nucleus accumbens inhibits social attachment and parental care in monogamous female prairie voles

“…Human studies have demonstrated that polymorphisms in the OXTR gene interact with early life adversity to predict quality of mothering and postpartum mood (Mileva-Seitz et al, 2013), in addition to adult emotion regulation and attachment style (Bradley et al, 2011). Experimental studies have demonstrated that OT circuits are sensitive to early social context, and early-life manipulation of these systems have long-term effects on later life social attachment behaviors (Ahern and Young, 2009; Ahern et al, 2011; Barrett et al, 2014). More recently, individual variation in NAcc OXTR density has been shown to interact with early-life social experiences to influence the ability to form partner preferences in adult prairie voles (Barrett et al, Under Revision).…”