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Objective To study the amelioration effect of glucocorticoid receptor (GR) antagonist mifepristone on the changes of learning and memory abilities in rat model of depression and explore mechanisms related.Methods In the present study, we used a 35-d rat chronic unpredictable stress (CUS) model to observe both depression-like behaviors in sucrose preference test (SPT) and open-field test (OFT) and learning and memory-associated behaviors in Morris water maze test.A total of 36 male adult Sprague-Dawley rats were randomly assigned to three groups of equal size: control group (CON); CUS group (CUS); CUS + mifepristone group (CM).Animals in CM group were first exposed to CUS for 14 d, and then were administered with 50 mg/kg per day of mifepristone with continued CUS procedure.Corticosterone EIA Kit was used to detect the concentration of plasma corticosterone (CORT).Nissl staining was used to observe the structure of hippocampus.Results The results demonstrate that CUS exposure induces both depressive-like and learning and memory-associated behaviors and that these deficits are reversed by mifepristone.Compared to CON group, the concentration of plasma CORT increased significantly in CUS group.We also found that CUS exposure damaged the structure of hippocampus, whereas mifepristone had an amelioration effect.Conclusion The results indicate that the structural deficits of hippocampus resulting from long-term stress exposure, which could contribute to the impairment of learning and memory in depression, are reversed by the GR receptor antagonist mifepristone.