Gender differences and effects of acute and chronic oxytocin on social interaction in mice

Abstract

BACKGROUND: Understanding emotion from others is an essential ability for the healthy development of all mammals. Anomalies in emotion processing are associated with developmental disorders such as schizophrenia and autism. Oxytocin is a nine amino-acid peptide (nonapeptide) hormone. It is well-known for its role in lactation and parturition, but it also has a key role in social recognition. Oxytocin has been suggested as a potential therapy in neurodevelopmental disorders such as schizophrenia and autism spectrum, however direct experimental investigation of the action of oxytocin is still limited. The aim of the present study was to explore acute and chronic dose-related effects of oxytocin on social interaction activity in male and female mice. METHODS: 8 week old adult C57BL/6N mice were obtained from the Laboratory Animal Unit at The University of Hong Kong. The experimental protocol was approved by the Committee on the Use of Live Animals for teaching and Research, University of Hong Kong (CULATR case NO: 2152-10). In the chronic administration group, a single injection of 10ug/kg, 100ug/kg, or 1000ug/kg oxytocin (Sigam-Aldrich) was given subcutaneously once a week for two weeks as part of a larger study on chronic effects of oxytocin. Social interaction test was conducted one week after the last oxytocin exposure. Mice received oxytocin injection 30min before test. In the acute administration group, another batch of mice was tested in the same way without previous exposure to oxytocin. Additional untreated mice received saline injection 30min before the social interaction test and were included as controls. The social interaction test conducted followed standard protocols in our lab. An experimental mouse paired with a “neutral” stimulus mouse from the same gender are tested together and scored as a single unit. The mice are put in opposite corners of the arena facing away from each other before the start of the 10-min social interaction test. Mice social interaction times were scored manually. RESULTS: In the control group, the male mice had longer social interaction time with strangers than female mice (P<0.05). In the oxytocin acute administration group, the social interaction time was increased with the increasing oxytocin doses in the female mice (P<0.05). There was a significant linear relationship between social interaction time and oxytocin doses. However, the oxytocin dose-effect curve showed an inverted U shape in the male mice. Both 100ug/kg and 1000ug/kg oxytocin increased social interaction activity in the male mice, but the maximal effect was obtained at 100ug/kg of oxytocin administration. In the oxytocin chronic administration, previous oxytocin exposures increased social interaction time in the female mice for all doses of oxytocin (P<0.05). The oxytocin dose-effect curve for the male mice in the chronic administration group had a similar inverted U shape as the acute administration, with the peak effect at 100ug/kg oxytocin administration (P<0.05). DISCUSSION: The social interaction measure in C57BL/6N mice is gender dependent. Male and female mice also have different responses to acute and chronic administration of oxytocin. Therefore, gender differences need to be carefully considered for further investigations into the utility of oxytocin.