Structural and functional sex differences in the ventral pallidal vasopressin system are associated with the sex-specific regulation of juvenile social play behavior in rats

The ventral pallidum (VP) has been implicated in the regulation of rewarding adult social behaviors, such as pair-bonding and sociosexual motivation. However, the role of the VP in regulating rewarding juvenile social behaviors, such as social play, is unknown. Social play is predominantly displayed by juveniles of many mammalian species and engagement in social play helps develop social competence. In this study, we determined whether the VP is involved in regulating social play in juvenile rats by temporarily inactivating the VP via bilateral infusions of muscimol, the GABAA receptor agonist. Muscimol treatment decreased social play duration in males and females compared to the same-sex control groups. We then focused on the vasopressin (AVP) system in the VP as one potential modulator of social play. We examined the organization of the AVP system in the VP in juvenile rats and found robust sex differences, with denser AVP-immunoreacive fibers and denser vasopressin 1a receptor (V1aR) binding in males compared to females, but a greater number of V1aR-expressing cells in females compared to males. Next, we determined whether exposure to social play changed the activation of V1aR-expressing VP cells in male and female juvenile rats. We found that exposure to social play enhanced the number of V1aR-expressing VP cells co-expressing fos , a marker of neuronal activation, in males only. Finally, we determined the causal involvement of AVP signaling in the VP in social play behavior by infusion of a specific V1aR antagonist into the VP prior to social play exposure. We found that V1aR blockade in the VP increased social play duration in juvenile male rats but decreased social play duration in juvenile female rats compared to same-sex control groups. These findings reveal structural and functional sex differences in the AVP system in the VP that are associated with the sex-specific regulation of juvenile social play behavior. ### Competing Interest Statement The authors have declared no competing interest.