Study M1122
Study name | Sun N 2022c |
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 reverse chronic mild stress (CMS)-induced depressive behaviors. 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 4 groups: (1) control group (non-stress with vehicle treatment), (2) CMS group (stress with vehicle treatment), (3) CMS + TAT-SERT-15C group (stress with TAT-SERT-15C treatment at the dose of 1.6 ug), and (4) CMS + fluoxetine group (stress with fluoxetine treatment at the dose of 2 ug). The CMS stress procedure lasted for 4 weeks, and drugs were microinjected into the DRN of mice after stress. The levels of serotonin, noradrenalin, and dopamine in the DRN were determined at 2 hours after microinjection using in vivo microdialysis combined with liquid chromatography-mass spectrometry (n=5-13/group). |
Study Type | Type1; Type2; |
Data available | Unavailable |
Organism | Mouse; C57BL/6J mouse; |
Categories of depression | Animal model; Chronic mild stress model; Chronic mild stress model; |
Criteria for depression | Sucrose preference test, forced swimming test, tail suspension test |
Sample size | 34 |
Tissue | Central; Brain; Dorsal raphe nucleus; |
Platform | MS-based; LC-MS: not reported; |
PMID | |
DOI | |
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 |
