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Journal of affective disorders

Journal of affective disorders

IF: 4.9
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Venlafaxine protects against chronic stress-related behaviors in mice by activating the mTORC1 signaling cascade

Published:1 November 2020 DOI: 10.1016/j.jad.2020.07.096 PMID: 32871684
Jin-Liang Wang , Yuan Wang , Ting-Ting Gao , Ling Liu , Ying-Jie Wang , Wei Guan , Ting-Ting Chen , Jie Zhao , Yin Zhang , Bo Jiang

Abstract

Background

Recent studies have suggested the role of mammalian target of rapamycin complex 1 (mTORC1) in the pathophysiology of depression. Although venlafaxine was thought to be a serotonin and norepinephrine reuptake inhibitor (SNRI), its pharmacological mechanism remain elusive. In this study, the effects of venlafaxine on the mTORC1 system were studied in both chronic unpredictable mild stress (CUMS) and chronic social defeat stress (CSDS) models.

Method

First, we examined whether repeated venlafaxine treatment reversed the effects of CUMS and CSDS on the mTORC1 signaling cascade in both the hippocampus and medial prefrontal cortex (mPFC). Second, several selective pharmacological inhibitors of the mTORC1 system, including rapamycin, LY294002 and U0126, were used together to determine whether the protective effects of venlafaxine against the CUMS and CSDS models were prevented by mTORC1 system blockade. Finally, genetic knockdown of mTORC1 by mTORC1-shRNA was further adopted to test whether mTORC1 was necessary for the anti-stress effects of venlafaxine in mice.

Result

Our results showed that the decreasing effects of CUMS and CSDS on the mTORC1 signaling cascade in the hippocampus and mPFC were restored by venlafaxine, and the use of rapamycin, LY294002, U0126 and mTORC1-shRNA fully abolished the anti-stress actions of venlafaxine in mice.

Conclusion

The mTORC1 system is involved in the pharmacological mechanism of venlafaxine.

Substances (10)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Rapamycin 53123-88-9 C51H79NO13 1034 suppliers $9.00-$6160.00
Rapamycin 53123-88-9 C51H79NO13 1034 suppliers $9.00-$6160.00
Rapamycin 53123-88-9 C51H79NO13 1034 suppliers $9.00-$6160.00
Rapamycin 53123-88-9 C51H79NO13 1034 suppliers $9.00-$6160.00
Venlafaxine 93413-69-5 C17H27NO2 265 suppliers $10.00-$3100.00
Venlafaxine 93413-69-5 C17H27NO2 265 suppliers $10.00-$3100.00
Venlafaxine 93413-69-5 C17H27NO2 265 suppliers $10.00-$3100.00
Venlafaxine 93413-69-5 C17H27NO2 265 suppliers $10.00-$3100.00
Rapamycin 53123-88-9 - Inquiry
Rapamycin 53123-88-9 - Inquiry

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