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Brain Research Bulletin

Brain Research Bulletin

IF: 3.5
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Imipramine exerts antidepressant-like effects in chronic stress models of depression by promoting CRTC1 expression in the mPFC

Published:1 November 2020 DOI: 10.1016/j.brainresbull.2020.08.028 PMID: 32905805
Ying-Jie Wang , Ling Liu , Yuan Wang , Jin-Liang Wang , Ting-Ting Gao , Hao Wang , Ting-Ting Chen , Wei Guan , Bo Jiang

Abstract

Recent studies have suggested that CREB-regulated transcription coactivator 1 (CRTC1) plays a role in the pathophysiology of depression. Although imipramine is thought to prevent the reuptake of synaptic serotonin and norepinephrine, its antidepressant-like mechanisms remain elusive. In this study, the effects of imipramine on CRTC1 were studied in several models of depression, including the chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS) and chronic social defeat stress (CSDS) models. We examined whether repeated imipramine administration can reverse the effects of CRS, CUMS and CSDS on CRTC1 expression in both the hippocampus and medial prefrontal cortex (mPFC). Furthermore, genetic knockdown of CRTC1 by CRTC1-shRNA was used to determine whether CRTC1 is necessary for the antidepressant-like effects of imipramine in mice. Our results showed that imipramine reversed the down-regulating effects of CRS, CUMS and CSDS on CRTC1 expression in the mPFC but not the hippocampus, and that CRTC1-shRNA fully abolished the antidepressant-like actions of imipramine in mice. In conclusion, CRTC1 in the mPFC is involved in the antidepressant mechanism of imipramine.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
IMIPRAMINE 50-49-7 C19H24N2 75 suppliers Inquiry
IMIPRAMINE 50-49-7 C19H24N2 75 suppliers Inquiry
IMIPRAMINE 50-49-7 C19H24N2 75 suppliers Inquiry
IMIPRAMINE 50-49-7 C19H24N2 75 suppliers Inquiry

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