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Study M1121

Study name

Sun N 2022b

Title

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

Overall design

The aim of this study was to examine whether dissociating serotonin transporter (SERT) from neuronal nitric oxide synthase (nNOS) in the dorsal raphe nucleus (DRN) could exert a fast-onset antidepressant effect. In this study, a peptide named TAT-SERT-15C was synthesized, in which the 15 C-terminal amino acids of SERT (SERT-15C) were N-terminally fused to the transduction domain of the Tat protein from the HIV type 1. C57BL/6J mice were divided into the following 2 groups: (1) control group (vehicle treatment), and (2) TAT-SERT-15C group (TAT-SERT-15C treatment at the dose of 1.6 ug). TAT-SERT-15C was microinjected into the DRN of mice, which produced an antidepressant-like effect. The levels of serotonin, noradrenalin, and dopamine in the DRN were determined at 2 hours using in vivo microdialysis combined with liquid chromatography-mass spectrometry (n=5/group).

Study Type

Type3;

Data available

Unavailable

Organism

Mouse; C57BL/6J mouse;

Categories of depression

Healthy individuals; Healthy individuals; Healthy individuals;

Criteria for depression

Forced swimming test, tail suspension test

Sample size

10

Tissue

Central; Brain; Dorsal raphe nucleus;

Platform

MS-based; LC-MS: not reported;

PMID

36302033

DOI

10.1126/science.abo3566

Citation

Sun N, Qin YJ, Xu C, et al. Design of fast-onset antidepressant by dissociating SERT from nNOS in the DRN. Science. 2022 Oct 28;378(6618):390-398.

Metabolite

Serotonin;