Background
Oxytocin (OT) attenuates the impairment in social behavior, a core symptom of psychiatric disorders, in a sex-dependent manner. Recently, we revealed that the therapeutic effect of OT differed dose-independently in depression model of female mice. However, it is remains unclear whether OT also exerts the unique effect on females under non-stress conditions. Thus, we investigated the effect of OT administration on the social behavior and hippocampal astrocytes expression levels, a key regulator for social behavior, in healthy female mice.
Methods
Adult female C57BL/6J mice were intraperitoneally injected with OT (0.01, 0.1, or 1.0 mg/kg) for 3 weeks. To assess the effects of OT treatment on social behavior, mice were subjected to the social interaction test (SIT). Then, hippocampal samples of mice were collected, and glial fibrillary acidic protein (GFAP) levels, an astrocyte marker, were evaluated by western blotting analysis.
 
Results
OT (0.01 mg/kg) group showed a significantly lower social interaction rate in the SIT and GFAP levels in the hippocampus than the vehicle group. The social interaction rate and GFAP levels of OT (0.1 and 1.0 mg/kg) groups were comparable to the vehicle group.
Discussion
Social behaviors require OT signaling in the hippocampus. Previous studies showed that astrocytic OT signaling modulated neuronal activity. These results suggest that low dose of OT (0.01 mg/kg) may have deleterious effects on social behavior and hippocampal astrocytes in health females.