Design of fast-onset antidepressant by dissociating SERT from nNOS in the DRN

Autor:	Nan Sun, Ya-Juan Qin, Chu Xu, Tian Xia, Zi-Wei Du, Li-Ping Zheng, An-an Li, Fan Meng, Yu Zhang, Jing Zhang, Xiao Liu, Ting-You Li, Dong-Ya Zhu, Qi-Gang Zhou
Rok vydání:	2022
Předmět:	Dorsal Raphe Nucleus Serotonin Plasma Membrane Transport Proteins Mice Depressive Disorder Major Multidisciplinary Drug Design Animals Nitric Oxide Synthase Type I Antidepressive Agents
Zdroj:	Science (New York, N.Y.). 378(6618)
ISSN:	1095-9203
Popis:	Major depressive disorder (MDD) is one of the most common mental disorders. We designed a fast-onset antidepressant that works by disrupting the interaction between the serotonin transporter (SERT) and neuronal nitric oxide synthase (nNOS) in the dorsal raphe nucleus (DRN). Chronic unpredictable mild stress (CMS) selectively increased the SERT-nNOS complex in the DRN in mice. Augmentation of SERT-nNOS interactions in the DRN caused a depression-like phenotype and accounted for the CMS-induced depressive behaviors. Disrupting the SERT-nNOS interaction produced a fast-onset antidepressant effect by enhancing serotonin signaling in forebrain circuits. We discovered a small-molecule compound, ZZL-7, that elicited an antidepressant effect 2 hours after treatment without undesirable side effects. This compound, or analogous reagents, may serve as a new, rapidly acting treatment for MDD.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8f12050f73c1085efd0e973e24048e90 https://pubmed.ncbi.nlm.nih.gov/36335277 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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