Differential behavioral effects of systemic oxytocin receptor blockade across social tasks and hierarchical ranks in male mice

Abstract

Oxytocin receptor signaling has been implicated in diverse social behaviors, but whether its behavioral effects depend on social tasks and an individual's position within a hierarchy remains unclear. We examined the effects of systemic administration of L-368,899, a blood-brain barrier-penetrating oxytocin receptor antagonist, across four domains of social behavior in male C57BL/6J mice: social rank, sex preference, general social preference, and dyadic interaction. Following the establishment of stable hierarchies in the tube test, administration of L-368,899 (10 mg/kg, intraperitoneally) to first-ranked mice did not alter their hierarchical position. Rank fluctuations were observed more frequently when the antagonist was administered to second-ranked mice. In both rank conditions, the remaining cage mates received saline. In the sex-preference task, saline-treated males spent more time in the female stimulus zone than in the male stimulus zone, whereas this preference was not statistically detectable following treatment with L-368,899 (3 or 10 mg/kg). In contrast, L-368,899 did not significantly alter proximity-based preference for a novel male over a nonsocial object or affect contact duration and inter-individual distance during dyadic interactions between familiar male cage mates, in which both members of each pair received the same treatment. Thus, systemic oxytocin receptor blockade did not produce a generalized reduction in social approach. Instead, the observed behavioral patterns suggest that its effects depend on specific social behavioral tasks and hierarchical position. These findings provide a pharmacological basis for further investigation of the task- and rank-dependent contributions of oxytocin receptor signaling to social behavior.

The authors' abstract, as published at the source. Pharmacology Biochemistry and Behavior, 2026 · DOI ↗