Ketamine induced gut microbiota dysbiosis and barrier and hippocampal dysfunction in rats.
Lei Xie, Zelin Zhuang, Baowen Guo, Yuehua Huang, Xiaoyan Shi, Zikai Huang, Ziquan Xu, Yanbin Chen, Yuyin Cao, Yanmin Zheng, Renhua Wu, Shuhua Ma
iScience November 15, 2024 DOI: 10.1016/j.isci.2024.111089 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | Ketamine |
| Topics | Ketamine Esketamine |
| Keywords | Drugs Microbiome Physiology Gut-brain-axis Psychopharmacology |
| Citations | 5 |
| Key findings | Ketamine addiction in rats is associated with gut microbiota disorders, intestinal barrier dysfunction, and altered hippocampal function, with correlations between gut bacteria abundance and addiction-related measures. |
Abstract
The microbiota-gut-brain axis (MGBA) plays a pivotal role in drug addiction. However, the pathophysiological mechanism of MGBA in ketamine addiction remains elusive. The present study investigated the ketamine-induced gut microbiota disorders, intestinal barrier dysfunction, and the alterations in brain function, using a conditioned place preference (CPP) model of ketamine addiction in rats. Compared with the control group, ketamine induced decreased amplitude of low-frequency fluctuation (ALFF) values in the hippocampus, and pyknotic nuclei and concentrated cytoplasm in hippocampal neurons, as well as alterations in gut microbiota composition, shortened ileum villi, and thinner colonic mucosa. We also found that the abundance of gut microbiota exhibited correlations with CPP score, hippocampal ALFF value, length of ileum villi, and thickness of colonic mucosa. Our findings provide evidence for abnormal alterations in the MGBA of ketamine-addicted rats, which improves our understating of the mechanism of ketamine addiction and the potential for developing new therapeutic strategies.
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
Cited by 2
- Pleiotropic modulation of the gut-brain-lung axis by ketamine and its enantiomers. Molecular Psychiatry April 13, 2026
- Inulin ameliorates chronic ketamine-induced anxiety-like behaviors and impairments in spatial learning and memory: involvement of gut microbiota, microbial metabolite short-chain fatty acids, and the BDNF-TrkB-ERK1/2-CREB pathway Frontiers in Microbiology April 7, 2026