Study M1124
Study name | Sun N 2022e |
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) of chronic mild stress (CMS) model 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 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. Then the levels of serotonin, noradrenalin, and dopamine in the mPFC and vHPC were determined at 24 hours after microinjection using in vivo microdialysis combined with liquid chromatography-mass spectrometry (n=9-12/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 | 40 |
Tissue | Central; Brain; Ventral hippocampus; Central; Brain; Medial prefrontal cortex; |
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 |
