Social play is a highly rewarding and motivated behavior predominately displayed by juveniles and expressed by nearly all mammalian species. Prior work suggested that the vasopressin (AVP) and oxytocin (OT) systems can regulate the expression of social play in sex-specific ways. Here we investigated whether there are sex differences in the recruitment of vasopressinergic and oxytocinergic brain regions following social play exposure in juvenile rats. Single-housed rats were allowed to play, in their home cage, with an age- and sex-matched unfamiliar conspecific for 10 min, or received similar handling but no partner. Double-labeled fluorescent immunohistochemistry for Fos and either AVP or OT was completed in adjacent series of tissue to determine recruitment of AVP- and OT-immunoreactive neurons in response to social play. Exposure to social play did not increase recruitment of AVP or OT neurons in the supraoptic (SO) or paraventricular (PVH) hypothalamic nuclei of either sex compared to the no-play control condition. Interestingly, there was a robust sex difference in SO recruitment, irrespective of social play condition, with males exhibiting twice the recruitment of SO-AVP and SO-OT neurons compared to females. Lastly, exposure to social play increased recruitment of the posterior bed nuclei of the stria terminalis (pBST) and the posterodorsal medial amygdalar nucleus (MEApd) compared to the no-play control condition, and this effect was most pronounced in females. Our findings revealed sex differences in the recruitment of brain regions (i) independent of play condition (i.e., SO) possibly representing a sex difference in the baseline levels of AVP and OT signaling required for typical functioning and (ii) specific to play condition (i.e., pBST, MEApd). In sum, this study provides further evidence that the neural substrates underlying social play behavior are sex-specific. This article is protected by copyright. All rights reserved.

Social play is a highly rewarding and motivated behaviour displayed by juveniles of many mammalian species. We hypothesized that the orexin/hypocretin (ORX) system is involved in the expression of juvenile social play behaviour because this system is interconnected with brain regions that comprise the social behaviour and mesocorticolimbic reward networks. We found that exposure to social play increased recruitment of ORX-A neurons in juvenile rats. Furthermore, central administration of ORX-A decreased social play duration, while central blockade of ORX-1 receptors differentially altered social play duration in juvenile rats with low versus high baseline levels of social play (increasing social play in low baseline social play individuals and decreasing social play in high baseline social play individuals). Together, our results provided the first evidence of a role for the ORX system in the modulation of juvenile social play behaviour.

Biographical note:Christina J. Reppucci: Christina J. Reppucci is a Postdoctoral Researcher in the Neurobiology of Social Behaviour Lab. Her research is focused on delineating the functional neural circuitry underlying motivated behaviours (e.g., social behaviour, feeding behaviour) using system neuroscience approaches, and assessing whether that circuitry is differentially recruited in males and females. Cassandra K. Gergely: Cassanda K. Gergely was an Undergraduate Thesis Student in the Neurobiology of Social Behaviour Lab whose research focused on quantifying the activation of neuropeptide populations during juvenile social play behaviour. Remco Bredewold: Remco Bredewold is a Senior Research Associate in the Neurobiology of Social Behaviour Lab. His research interests focus on the roles of vasopressin and oxytocin in the development of social behaviour. More specifically, he is studying juvenile social play and social recognition. Alexa H. Veenema: Alexa H. Veenema is an Associate Professor of Psychology, and the Director of the Neurobiology of Social Behaviour Lab at Michigan State University. Her research focuses on the neural basis of social behaviour. Understanding the regulation of social behaviour is essential to gain insights in normal social functioning as well as in abnormal social functioning as observed in e.g. autism spectrum disorder, personality disorders, mood and anxiety disorders, and schizophrenia. Her ultimate goal is to understand and treat the causes of social behaviour deficits more effectively.Social play is a highly rewarding and motivated behaviour displayed by juveniles of many mammalian species. We hypothesized that the orexin/hypocretin (ORX) system is involved in the expression of juvenile social play behaviour because this system is interconnected with brain regions that comprise the social behaviour and mesocorticolimbic reward networks. We found that exposure to social play increased recruitment of ORX-A neurons in juvenile male and female rats. Furthermore, central administration of ORX-A decreased social play expression in both sexes, while central blockade of ORX-1 receptors differentially altered social play expression in rats with low versus high baseline levels of social play. Together, our results provided the first evidence of a role for the ORX system in the modulation of juvenile social play behaviour.