Background
Depression is twice as common in women as in men. Glucocorticoid (GC) exposure is a major risk factor for depression. Oxytocin (OT) has been shown to exert antidepressant-like effect via enhancement of CREB-BDNF pathway in the hippocampus, a key factor of mood regulation. However, it is remains unclear whether the hippocampal CREB-BDNF pathway is related to the antidepressant-like effect of OT under conditions of GC exposure, particularly in the dexamethasone (DEX)-induced depression model of female mice.
Methods
Female C57BL/6J mice were used in this study. All mice were administered with either saline (vehicle), DEX (5 mg/kg), or OT (1 mg/kg) + DEX (5 mg/kg) for eight weeks. After the termination of drug administration, animals were assessed of depression-like behavior by forced swimming test (FST). The day after the FST, the mice were sacrificed under anesthesia and their hippocampus were evaluated for phosphorylated CREB (p-CREB) and BDNF protein levels by western blot analyses.
Results
OT+DEX mice showed a significantly lower immobility time compared to the DEX mice in the FST. The immobility time of OT+DEX group was comparable with the vehicle group. In the hippocampus, BDNF and p-CREB protein levels were significantly higher in the OT+DEX group than in the vehicle and DEX groups.
Discussion
Simultaneous OT treatment blocked the adverse effects of DEX. OT treatment upregulated p-CREB and BDNF levels of the DEX exposed hippocampus. These results suggest OT exerts its antidepressant-like effect by activating the hippocampal CREB-BDNF signaling pathway in female.