CONTEXT-DEPENDENT EFFECTS OF INTRAPERITONEAL INJECTIONS OF OXYTOCIN RECEPTOR ANTAGONIST ON SOCIAL RANK AND OTHER SOCIAL BEHAVIOR IN MICE
Authors: Matsushima *Shuntaro , Nasukawa Daiki , Yamada Kota , Hirakata Haruka , Tamura Ryuto , Yatagai Saya , Hayashi Kazuko , Ujihara Yusuke , Toda Koji 
Published: February 2025

Abstract

Background
Social rank is formed through interactions with other individuals and experiences in the community. The existence of social rank helps animals avoid unnecessary conflicts, reduce energy costs spent in competing for limited resources, and secure comfortable living spaces. Thus, social rank has a profound impact on an individual’ s survival, reproductive success, health, and other behaviors. Despite their importance to societies and individuals, the psychological and neurobiological mechanisms underlying social rank remain unclear. Oxytocin has received increasing attention for its role in social behaviors. Oxytocin is involved in a variety of social behavior, including pair-bonding, maternal behavior, aggression, social decision making, observational fear conditioning, and social recognition in many species. Oxytocin is emerging as a candidate pharmacological target for the treatment of mental disorders, especially those with social dysfunction, such as autism spectrum disorder, social anxiety disorder, and schizophrenia.

Aims & Objectives
The causal relationship between oxytocin levels and social rank remains unclear. Here, we examined the effects of intraperitoneal administration of a blood-brain barrier penetrating oxytocin receptor antagonist, L-368,899, on various social behaviors.

Method
First, we examined the effect of intraperitoneal injection of oxytocin receptor antagonist (10 mg/kg) on the tube test to examine the causal relationship between oxytocin and social rank. Second, we examined the effect of the oxytocin receptor antagonist (3 mg/kg and 10 mg/kg) on sex preference to validate the effect of the oxytocin antagonist on the discrimination of other individuals and on social interaction, and to rule out the possibility that the oxytocin receptor antagonist is not working. Third, we examined the effect of oxytocin antagonists (10 mg/kg) on a social preference task with unfamiliar male mice and direct dyadic interactions between familiar male mice in an open-field box.

Results
In the tube test, injection of the oxytocin receptor antagonist did not affect first-rank mice, but caused fluctuation of the rank in second-rank mice, suggesting that the function of oxytocin in the maintenance of the social rank is rank-dependent. Second, injection of the oxytocin receptor antagonist dose- dependently impaired the sex preference of the male mice, confirming that oxytocin is essential in sexual behavior. Third, injection of the oxytocin receptor antagonist did not affect social preference and dyadic interaction between the male mice, suggesting that oxytocin is not necessary for direct social interaction.Discussion &ConclusionOur results demonstrate that the role of oxytocin in male mice is limited to a specific context of social behavior. Our findings pave the way to understanding the relationship between oxytocin receptors and social behavior.

Discussion & Conclusion
Our results demonstrate that the role of oxytocin in male mice is limited to a specific context of social behavior. Our findings pave the way to understanding the relationship between oxytocin receptors and social behavior.