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.

Iscience
|November 4, 2024
PubMed

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.