Oxytocin treatment improves dexamethasone‐induced depression‐like symptoms associated with enhancement of hippocampal CREB‐BDNF signaling in female mice

AIMS: Chronic stress and glucocorticoid exposure are risk factors for depression. Oxytocin (OT) has been shown to have antistress and antidepressant‐like effects in male rodents. However, depression is twice as common in women than in men, and it remains unclear whether OT exerts antidepressant‐like effects in women with depression. Therefore, in this study, we investigated the therapeutic effect of chronic OT administration in a female mouse model of dexamethasone (DEX)‐induced depression. METHODS: Female C57BL/6J mice were administered saline (vehicle, s.c.), DEX (s.c.), or OT (i.p.) + DEX (s.c.) daily for 8 weeks, and then assessed for anxiety‐ and depression‐like behaviors. We also examined the hippocampal levels of phosphorylated cAMP response element‐binding protein (p‐CREB) and brain‐derived neurotrophic factor (BDNF), which are important mediators of the response to antidepressants. RESULTS: Simultaneous OT treatment blocked the adverse effects of DEX on emotional behaviors. Furthermore, it upregulated p‐CREB and BDNF in the hippocampus. CONCLUSION: OT may exert antidepressant‐like effects by activating hippocampal CREB‐BDNF signaling in a female mouse model of depression.