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Study M1123

Study name

Sun N 2022d

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 increasing of intercellular serotonin in the dorsal raphe nucleus (DRN) may reduce serotonin release into the medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC). 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 3 groups: (1) control group, (2) TAT-SERT-15C group (TAT-SERT-15C treatment at the dose of 1.6 ug), and (3) fluoxetine group (fluoxetine treatment at the dose of 2 ug). Drugs were microinjected into the DRN of mice, then the levels of serotonin, noradrenalin, and dopamine in the DRN, mPFC, and vHPC were determined at 24 hours after microinjection using in vivo microdialysis combined with liquid chromatography-mass spectrometry (n=9/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

27

Tissue

Central; Brain; Ventral hippocampus;

Central; Brain; Dorsal raphe nucleus;

Central; Brain; Medial prefrontal cortex;

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;