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

Horm Behav. 2026 May 20;182:105949. doi: 10.1016/j.yhbeh.2026.105949. Online ahead of print.

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 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), PVN^OXT 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 SON^OXT cell bodies nor chemogenetic stimulation of PVN^OXT projections to the NAc altered juvenile social play but increased social investigation. However, chemogenetic stimulation of PVN^OXT 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 NAc^OXTR neurons, an effect driven by males. Together, these findings suggest that distinct OXT neuronal populations modulate different forms of social behavior and that PVN^OXT neurons and OXT signaling in the NAc sex-specifically modulate social play behavior.

PMID:42160788 | DOI:10.1016/j.yhbeh.2026.105949