Ketamine alleviating depressive-like behaviors is associated with regulation of nNOS–CAPON–Dexras1 complex in chronic unpredictable mild stress rats
Yiwei Shen, Feng Lv, Su Min, Xuechao Hao, Jian Yu
Translational Neuroscience September 21, 2022 DOI: 10.1515/tnsci-2022-0245 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled animal experiment Peer reviewed |
|---|---|
| Sample size | 48 |
| Population | Rats: healthy controls and a chronic unpredictable mild stress (CUMS) model of depression |
| Intervention | Ketamine |
| Dose | 10 mg/kg |
| Duration | 3 days of ketamine treatment |
| Measures | Sucrose preference test, open field test, immunohistochemistry, immunofluorescence, real-time PCR |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine at 10 mg/kg for 3 days improved depressive-like behavior in CUMS rats, increasing total distance traveled, rearing counts, sucrose preference, and prefrontal cortex CAPON and Dexras1 expression while decreasing nNOS expression. The authors suggest these effects may be related to reduced nNOS and enhanced CAPON and Dexras1 signaling. |
Abstract
Abstract:
Background: A growing number of studies have demonstrated that ketamine induces rapid and sustained antidepressant action. Neuronal nitric oxide synthase (nNOS) signaling has been explored for the treatment of neuropsychiatric disorders for decades. But the effect of ketamine on nNOS signaling is poorly understood. The aim of the present study was to investigate the effect of ketamine on nNOS signaling in a chronic unpredictable mild stress (CUMS) model of depression.
Methods: Forty-eight rats were randomly divided into four groups: the control group of healthy rats (group C), the healthy rats treated with ketamine 10 mg/kg for 3 days (group CK), the rats model of stress-induced depression group (group D), and the depressed group treated with ketamine 10 mg/kg for 3 days (group DK). The sucrose preference test and open field test were used to assess behavioral changes. Immunohistochemistry, immunofluorescence, and real-time PCR analysis were carried out to measure the expression of nNOS, CAPON, and Dexras1 in the prefrontal cortex (PFC) of the CUMS rats.
Results: Compared with healthy rats, the total distance traveled, the rearing counts, the sucrose preference percentage (SPP), and CAPON and Dexras1 expression in the PFC significantly decreased, while nNOS expression increased in CUMS rats. After treating with ketamine, the total distance traveled, the rearing counts, the SPP, and CAPON and Dexras1 expression significantly increased, while nNOS expression significantly decreased.
Conclusion: The results indicated that ketamine improved the depressive behavior of rats, which may be related to the reduced nNOS expression and enhanced CAPON and Dexras1 expression.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 6
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry 2018
- Intermittent administration of low dose ketamine can shorten the course of electroconvulsive therapy for depression and reduce complications: A randomized controlled trial. Psychiatry Research November 1, 2019
- NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses Nature June 15, 2011
and 1 more in the library