Effects of (S)-ketamine on depression-like behaviors in a chronic variable stress model: a role of brain lipidome
Cui-Hong Zhou, Xinxin Zhao, Xinxu Ma, Hongzhe Ma, Rui Li, Guangtao Hu, Hua-ning Wang, Z. Peng, Min Cai
Frontiers in Cellular Neuroscience February 15, 2023 DOI: 10.3389/fncel.2023.1114914 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experiment Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | (S)-ketamine |
| Dose | single sub-anesthetic dose |
| Topics | Depression Esketamine Ketamine |
| Key findings | (S)-ketamine partially normalized stress-induced lipid disturbances in the hippocampus, correlating with reversal of depressive-like behaviors in mice. |
Abstract
Introduction: Compelling evidence indicates that a single sub-anesthetic dose of (S)-ketamine elicits rapid and robust antidepressant effects. However, the underlying mechanisms behind the antidepressant effects of (S)-ketamine remain unclear.
Methods: Here, using a chronic variable stress (CVS) model in mice, we analyzed changes inthe lipid compositions of the hippocampus and prefrontal cortex (PFC) with a mass spectrometry-based lipidomic approach.
Results: Similar to previous research outcomes, the current study also showed that (S)-ketamine reversed depressive-like behaviors in mice produced by CVS procedures. Moreover, CVS induced changes inthe lipid compositions of the hippocampus and PFC, notably in the contents of sphingolipids, glycerolipids, and fatty acyls. With the administration of (S)-ketamine, CVS-induced lipid disturbances were partially normalized, particularly in the hippocampus.
Conclusion: Altogether, our results indicated that (S)-ketamine could rescue CVS-induced depressive-like behaviors in mice through region-specific modulation of the brain lipidome, contributing to the understanding of (S)-ketamine’s antidepressant effects.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
Cited by 6
- Evidence from preclinical and clinical metabolomics studies on the antidepressant effects of ketamine and esketamine. Neuroscience Letters May 14, 2024
- Esketamine alleviates LPS-induced depression-like behavior by activating Nrf2-mediated anti-inflammatory response in adolescent mice. Neuroscience February 16, 2025
- Effects of esketamine and fluoxetine on depression-like behaviors in chronic variable stress: a role of plasma inflammatory factors. Frontiers in Psychiatry 2024
- Targeting TLR4/PPARα-mediated neuroinflammation in the prefrontal cortex: S-ketamine and S-HNK rapidly alleviate depression-like behaviors Journal of Neuroimmunology July 1, 2026
- Repeated 7-day exposure to ketamine induces anxiety-like behaviors and neuronal apoptosis in mice via DRD1-medicated inhibition of Akt/Gsk-3β phosphorylation. Cell Biology and Toxicology January 30, 2026
and 1 more in the library
Cites 10
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
and 5 more in the library