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

ABSTRACT 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 competency. 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 PVNOXT projections to the NAc altered the expression of juvenile social play but instead increased social investigation. However, chemogenetic stimulation of PVNOXT cell bodies as well as intra-NAc infusion of OXT 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 NAc-OXT signaling sex-specifically modulate social play behavior. Competing Interest Statement The authors have declared no competing interest.