Dose-dependent anxiolytic and antidepressant-like effects of chronic oxytocin in corticosterone-induced female mouse model of anxiety and depression

Oxytocin (OXT) has therapeutic effects on psychiatric disorders, such as anxiety and depression, in both animals and humans; however, an increasing number of OXT treatment studies have reported conflicting results. Although the effects of OXT on emotion regulation vary depending on factors such as sex and dosage, the dose-dependent effects of chronic OXT administration remain unclear, particularly in women. In this study, we aimed to assess the dose-dependent effects of chronic OXT administration on emotional behavior in female mice with corticosterone (CORT)-induced anxiety and depression. A total of 58 female C57BL/6J mice received daily co-administration of OXT (0.1 or 1 mg/kg, intraperitoneal) and/or CORT (40 mg/kg, subcutaneous) for 4 weeks, and their anxiety- (open field and elevated plus maze tests) and depression-like behaviors (forced swimming and tail suspension tests) were evaluated. A 0.1 mg/kg dose of OXT blocked the CORT-induced increase in anxiety-like behavior (open field test) and depression-like behavior (forced swimming test), whereas the 1 mg/kg dose did not. Similarly, a dose-dependent effect of OXT was observed in the elevated plus maze and tail suspension tests. Furthermore, the 1 mg/kg dose of OXT significantly increased plasma OXT levels. These findings suggest that a certain level of OXT signaling activity is needed to exert anxiolytic and antidepressant-like effects, which may lead to a non-linear dose-dependent effect of OXT in a female mouse model of CORT-induced anxiety and depression. Targeting dose-dependent OXT signaling is a potential therapeutic strategy for women with psychiatric disorders. • Simultaneous oxytocin (0.1 mg/kg) blocked the aversive effects of corticosterone. • Simultaneous oxytocin (1 mg/kg) exerted any effects on emotional behaviors. • Simultaneous oxytocin (1 mg/kg) elevated peripheral oxytocin levels. • Oxytocin regulated emotion in a non-linear dose-dependent manner in female mice.