Effects of Oxytocin Administration on Social Behavior in Male and Female Mice

Abstract

Oxytocin has been well used in animal studies to determine its role in social behavior. However, the route of administration between studies often differs posing challenges in generalizing results. Additionally, oxytocin has been found to differentially affect male and female animals. The current study aims to compare routes of administration of the same dose of oxytocin and its effects on social and anxiety-like behaviors across male and female mice. Adult C57BL/6J mice were chronically pretreated with saline or oxytocin (12 μg) for 14 consecutive days, a dosage previously shown to alter prosocial and anxiety-like behavior in mice. Mice received either intranasal (i.n., 12 ml, 6 ml per nostril) or intraperitoneal (i.p., 120 ml) administration. On the fourteenth dosing day, mice completed the elevated plus maze (EPM) followed by the three-chamber sociability task (3C), and the free dyadic social interaction (FDSI) in a 24-hour completion cycle. General and social anxiety-like behaviors, social preference, and social novelty were coded utilizing Noldus EthoVision XT and human coders. Our results suggest that female and male mice have differing anxiety-like and social behavior after OT treatment, and that male mice are more susceptible to stress and behavioral changes depending on the route of peripheral administration route. These findings suggest that sex differences and route of oxytocin administration play an intricate role in anxiolytic and sociability behavior modulation.