Schisandrin rescues depressive-like behaviors induced by chronic unpredictable mild stress via GDNF/ERK1/2/ROS and PI3K/AKT/NOX signaling pathways in mice

The current study aimed to prove the antidepressant-like effects and the probable mechanisms of Schisandrin on depression, which induced by chronic unpredictable mild stress (CUMS) in mice. Four weeks of CUMS exposure resulted in depressive-like behavior, as indicated by the significant decrease in sucrose consumption and increase the immobility time in the forced swim test, but without any influence on the locomotor activity. Further, there were significant downregulations of GDNF/ERK1/2/ROS and PI3K/AKT/NOX signaling pathways in the hippocampus and prefrontal cortex in depressed mice. Treatment of mice with Schisandrin (30 mg/kg) and Fluoxetine (10 mg/kg) significantly ameliorated all the behavioral and biochemical changes induced by CUMS. These results suggest that Schisandrin produces an antidepressant-like effect in CUMS-induced mice, which possibly mediated, at least in part, by rectifying the signaling pathways of GDNF/ERK1/2/ROS and PI3K/AKT/NOX.