Differential effects of oxytocin receptor antagonist on social rank and other social behavior in male mice

Social rank within a group is essential for survival in many animals. Rank in the community helps to avoid unnecessary conflicts and establish stable relationships with others. Oxytocin has received increasing attention for its function in social behavior. However, the causal relationship between oxytocin receptor signaling and social rank remains unclear. Here, we examined the effects of intraperitoneal administration of the blood-brain barrier-penetrating oxytocin receptor antagonist L-368-899 on (1) social rank, (2) sex preference, (3) social preference, and (4) dyadic interaction in male mice. In the tube test, oxytocin receptor blockade had no effect on first-rank mice but increased rank fluctuations in second-rank mice, suggesting that oxytocin receptor signaling contributes to the stability of intermediate social rank. In addition, oxytocin receptor blockade impaired sex preference without affecting general social preference or dyadic interactions between familiar male mice. These findings indicate that oxytocin receptor signaling selectively contributes to specific forms of social behavior rather than broadly regulating all social interactions. Overall, our results demonstrate that the role of oxytocin receptor signaling in male mice is highly context-dependent.