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.