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Published on: September 19, 2019
Ketamine induced gut microbiota dysbiosis and barrier and hippocampal dysfunction in rats
Lei Xie1,2, Zelin Zhuang1,2, Baowen Guo1,2
1Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, China.
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.
Insights
Ketamine addiction disrupts the gut-brain axis, altering gut microbiota and brain function in rats. These changes highlight potential therapeutic targets for treating ketamine addiction.
Area of Science:
- Neuroscience
- Microbiology
- Pharmacology
Background:
- The microbiota-gut-brain axis (MGBA) is crucial in drug addiction.
- The specific mechanisms of MGBA in ketamine addiction are not well understood.
Purpose of the Study:
- To investigate ketamine-induced gut microbiota disorders.
- To examine intestinal barrier dysfunction.
- To analyze alterations in brain function within a rat model of ketamine addiction.
Main Methods:
- Utilized a conditioned place preference (CPP) model in rats to study ketamine addiction.
- Assessed gut microbiota composition and intestinal morphology (ileum villi length, colonic mucosa thickness).
- Measured brain function using amplitude of low-frequency fluctuation (ALFF) in the hippocampus and examined hippocampal neuron morphology.
Main Results:
- Ketamine exposure led to decreased hippocampal ALFF values and neuronal changes.
- Significant alterations in gut microbiota composition were observed.
- Intestinal barrier dysfunction was evidenced by shortened ileum villi and thinner colonic mucosa.
- Gut microbiota abundance correlated with CPP score, hippocampal ALFF, and intestinal parameters.
Conclusions:
- Ketamine addiction is associated with abnormal alterations in the microbiota-gut-brain axis in rats.
- These findings enhance the understanding of ketamine addiction mechanisms.
- The study suggests potential for novel therapeutic strategies targeting the MGBA for ketamine addiction treatment.
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