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Background: Depression is an emotional disorder characterized by depression, lack of pleasure, and cognitive and sleep disorders. It is a systemic disease with a complex pathogenesis. In this study, we will be focused to investigate their associations and the exact functional mechanisms of miR-382-5p and NR3C1 in depression. Materials and Methods: We measured the expressions of microRNA-382-5p (miR-382-5p) and NR3C1 in the hippocampus by chronic unpredictable mild stress (CUMS). Depression behavior test including novelty-suppressed feeding test (NSFT), sucrose preference test (SPT), and forced swim test (FST) on rats have been conducted to examine the roles and functions of miR-382-5p and NR3C1 on depression-like behaviors by lentivirus vectors. Results: Up-regulation of miR-382-5p and down-regulation of NR3C1 were observed in rats' hippocampus induced by CUMS. miR-382-5p targeted NR3C1 and inhibited the expressions of NR3C1 in rats' hippocampus. miR-382-5p could significantly change the depression behaviors induced by CUMS. NR3C1 downstream BDNF and p-TrkB were also oppositely associated with miR-382-5p in rats' hippocampus. Conclusion: Through our experiments and analysis, we found that the associations between miR-382-5p and NR3C1 could affect the depression-like behaviors. [ABSTRACT FROM AUTHOR]