Results: The rats exhibited depressive-like behavior in the forced swim test, sucrose preference test, novelty-suppressed feeding test, and social interaction test. The expression of GRs and MRs decreased, and CRF levels increased in the PVN. Intra-PVN administration of RU486 increased the levels of GRs and CRF without influencing depressive- or anxiety-like behavior. The spironolactone-treated group exhibited an increase in MRs, and behavior improved in the novelty-suppressed feeding test and social interaction test, but the levels of GRs and CRF in the PVN and depressive-like behavior were unaltered. Interestingly, the combined intra-PVN administration of RU486 and spironolactone restored the expression of GRs, MRs, and CRF and improved depressive-like behavior.