The Antidepressant Effect of Magnolol on Depression-like Behavior of CORT-treated Mice

Although the antidepressant effect of magnolol has been revealed in previous reports, the mechanism remains unclear. In this study, the antidepressant effect of magnolol on corticosterone-induced (CORT-induced) depressed mice was investigated in vivo. After 21 days of CORT induction, the mice showed marked depressive-like behaviors, with a decrease in sucrose preference score and an increase in immobility time in tail suspension test (TST) and forced swimming test (FST). Pretreatment with either magnolol (50 mg/kg, i.p.) or the kappa opioid receptor (KOR) antagonist nor-BNI (10 mg/kg, i.p.) prevented CORT-induced depression-like behavior and reduced CORT-induced dynorphin (DYN A) elevation in the hippocampal DG. However, no depression-like behavior was observed in mice with KOR downregulation in the DG. We further found that upregulation of DYN A in the DG caused depression, which was blocked by intraperitoneal injection of nor-BNI and modulated by magnolol. The present study demonstrated that magnolol could ameliorate CORT-induced depression-like behaviors, by modulating the DYN A/KOR system in the DG of the hippocampus.