The MTOR Signaling Pathway Mediates The Antidepressant Effects Of Venlafaxine

Purpose The purpose of this is to show that whether the mTOR pathway participates in depression and whether it mediates the antidepressant effects of venlafaxine,proving that mTOR is a new target for antidepression.Methods In this study,first,we used depression models of C57BL/6J mice,Chronic Social Defeat Stress(CSDS)and Chronic Unpredictable Stress(CUMS),respectively.Secondly,the behavioral experiments of Forced swimming test(FST),Tail suspension test(TST),Sucrose preference test(SPT),Social interaction test and Western blotting were used to study whether the mTOR signaling pathway changed after the two models successfully simulated depression.Besides,the selective pharmacologcial inhibitor of mTOR,rapamycin,was used to determine if the protecting effects of venlafaxine against the CSDS and CUMS models were prevented by mTOR system blockade.Finally,immunofluorescence to test whether venlafaxine has antidepressant effect after silenced gene mTOR.So to verify that mTOR signaling pathway mediates the antidepressant effect of venlafaxine.Results Venlafaxine not only produced antidepressant effects in two depression models,but also reversed the CSDS-induced and CUMS-induced decrease of mTOR signalling pathway in the hippocampus and medial prefrontal cortex in mice.Rapamycin significantly blocked the antidepressant effects of venlafaxine in CSDS and CUMS.In addition,mTOR knockdown also abolished the antidepressant effects of venlafaxine in the two models.Conclusions These results indicate that the mTOR signaling pathway mediates the antidepressant effects of venlafaxine.