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Alterations in gut microbiota affect behavioral and inflammatory responses to methamphetamine in mice

Psychopharmacology (2022)Cite this article

Abstract

Rationale and objectives

Methamphetamine (METH) is a highly addictive and widely abused drug that causes severe neuroinflammation in the human brain. The gut microbiota has a tremendous impact on the core symptoms of neuropsychiatric disorders via the microbiota-gut-brain (MGB) axis. However, it is not clear whether alterations in the gut microbiota are involved in METH exposure.

Methods

We established a mouse model with chronic, escalating doses of METH exposure. Intervene in gut microbiota with antibiotics to observe the changes of locomotor activity caused by METH exposure in mice. qPCR and 16S rRNA gene sequencing were used to analyze the gut microbiota profiles. In addition, we tested the levels of inflammatory factors in the nucleus accumbens (NAc), prefrontal cortex (mPFC), hippocampus (HIp), and spleen. Finally, short-chain fatty acids (SCFAs) were supplemented to determine the interaction between behavior changes and the structure of gut microbiota.

Results

In this research, METH increased the locomotor activity of mice, while antibiotics changed the effect. Antibiotics enhanced the expression of pro-inflammatory cytokines in mPFC, HIp, and spleen of METH-exposed mice. METH altered the gut microbiota of mice after antibiotic treatment, such as Butyricicoccus and Roseburia, which are related to butyrate metabolism. Supplementation with SCFAs changed the behavior of METH-exposed mice and decreased Parabacteroides and increased Lactobacillus in METH-exposed mice gut.

Conclusions

This research showed that antibiotics affected the behavior of METH-exposed mice and promoted inflammation. Our findings suggest that SCFAs might regulate METH-induced gut microbiota changes and behavior.

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Funding

This work was supported by research grants from the National Natural Science Foundation of China (grant numbers 81871537).

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Authors and Affiliations

  1. Department of Immunology and Pathogenic Biology, College of Basic Medicine, Xi’an Jiaotong University Health Science Center, Xi’an, People’s Republic of China

    Simin Lai, Jing Wang, Biao Wang & Yanjiong Chen

  2. Forensic Medicine College, Key Laboratory of the Health Ministry for Forensic Medicine, Xi’an Jiaotong University, Xi’an, People’s Republic of China

    Rui Wang & Teng Chen

  3. National Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, the Second Affiliated Hospital of Xi’an Jiaotong University College of Medicin, Xi’an, People’s Republic of China

    Guodong Li

  4. Department of Laboratory Medicine, Baoji Maternal and Child Health Hospital, Baoji, People’s Republic of China

    Yuwei Jia

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  1. Simin Lai
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  2. Jing Wang
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  3. Biao Wang
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  4. Rui Wang
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Correspondence to Yanjiong Chen.

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Lai, S., Wang, J., Wang, B. et al. Alterations in gut microbiota affect behavioral and inflammatory responses to methamphetamine in mice. Psychopharmacology (2022). https://doi.org/10.1007/s00213-022-06154-0

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Keywords

  • Methamphetamine
  • Gut microbiota
  • Neuroinflammation
  • Short-chain fatty acids