Sex-specific regulation of social play in juvenile rats by oxytocin neurons in the hypothalamus and oxytocin signaling in the nucleus accumbens.

Social play is a rewarding behavior shown across juvenile mammalian species and is important for the development of social competency throughout the lifespan. The neuropeptide oxytocin (OXT) regulates various social behaviors and is being used in clinical trials to improve social functioning. However, the role of OXT in juvenile social play is largely unknown. To address this gap, we determined the involvement of hypothalamic OXT-producing neurons in the supraoptic nucleus (SON) and paraventricular nucleus (PVN), PVNOXT projections to the nucleus accumbens (NAc), and OXT signaling within the NAc, in the regulation of social play in juvenile male and female rats. We found that neither chemogenetic stimulation of SONOXT cell bodies nor chemogenetic stimulation of PVNOXT projections to the NAc altered juvenile social play but increased social investigation. However, chemogenetic stimulation of PVNOXT cell bodies as well as acute infusion of OXT into the NAc decreased social play in males without an effect in females. Lastly, social play duration correlated negatively with the proportion of activated NAcOXTR neurons, an effect driven by males. Together, these findings suggest that distinct OXT neuronal populations modulate different forms of social behavior and that PVNOXT neurons and OXT signaling in the NAc sex-specifically modulate social play behavior.