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Characterization of Gut Microbiota in Rats and Rhesus Monkeys After Methamphetamine Self-administration

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Abstract

Methamphetamine (MA) is one of the most abused drugs globally, but the mechanism of its addiction remains unclear. Several animal studies have shown that the gut microbiota (GM) influences addictive behaviors, but the pattern of GM changes during addiction in animals of different species remains unclear. The aim of this study was to explore the association between dynamic changes in GM and MA self-administration acquisition among two classical mammals, rhesus monkeys (Macaca mulatta) and rats, MA self-administration models. Male Sprague–Dawley rats and male rhesus monkeys were subjected to classical MA self-administration training, and fecal samples were collected before and after MA self-administration training, respectively. 16S rRNA sequencing was used for GM analyses. We found that GM changes were more pronounced in rats than in rhesus monkeys, as evidenced by more GM taxa producing significant differences before and after MA self-administration training in rats than in monkeys. We also found that the expression of the genus Clostridia_vadinBB60_group significantly decreased after MA self-administration training in both rats and rhesus monkeys. Lactobacillus changes were significantly negatively correlated with total MA uptake in rats (Pearson R =  − 0.666, p = 0.035; Spearman R =  − 0.721, p = 0.023), whereas its change was also highly negatively correlated with total MA uptake in rhesus monkeys (Pearson R =  − 0.882, p = 0.118; Spearman R =  − 1.000, p = 0.083), although this was not significant. These findings suggest that MA causes significant alterations in GM in both rhesus monkeys and rats and that the genus Lactobacillus might be a common therapeutic target for MA uptake prevention across the species.

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Data Availability

All sequencing data is available at PRJNA1026554.

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Funding

This work was supported by the National Natural Science Foundation of China(82271535), the Science and Technology Innovation Program of Hunan Province (2022RC1008), the Hunan Provincial Natural Science Foundation (2021JJ40894), the Changsha Natural Science Foundation Project (kq2014239), the Scientific Research Project of Hunan Provincial Health Commission (202103090528), the Innovation of Science and Technology 2030-Major Project “platform of non-human primate models” (2021ZD0200900), grants from the Lingang Lab (LG202106-03), the Brain Science and Brain-Like Intelligence Technology (2021ZD0202105), Shanghai “the Hospital Garden Star” Funding for training of young medical professionals (20224Z0017), and the National Natural Science Foundation of China (82171483). The authors report no biomedical financial interests or potential conflicts of interest.

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  1. Li He and Jia-hui Zhou contributed equally to this study.

Authors and Affiliations

  1. Department of Psychiatry and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China

    Li He, Huan Li, Tie-qiao Liu & Xiao-jie Zhang

  2. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Jia-hui Zhou, Wen-lei Zhang & Hai-feng Jiang

  3. Lingang Laboratory, Shanghai, 200031, China

    Rong-wei Zhai

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  1. Li He
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All the authors have read and approved the final manuscript. Jia-hui Zhou and Wen-lei Zhang conducted the monkey MA self-administration trials. Huan Li conducted the rat MA self-administration trials. Li He analyzed the data and drafted the manuscript. Jia-hui Zhou, Hai-feng Jiang, and Tie-qiao Liu reviewed and edited the manuscript. Rong-wei Zhai and Xiao-jie Zhang were responsible for the conceptualization, design, and review.

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Correspondence to Rong-wei Zhai or Xiao-jie Zhang.

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The use and care of rhesus monkeys (Macaca mulatta) complied with the guidelines of the Animal Advisory Committee at the Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences. The ethics application entitled “Cognitive-behavioral and neural circuitry of non-human primate models of schizophrenia, novel gene editing techniques and animal models of brain disorders in non-human primates, cortical developmental mechanisms and non-human primate models of related diseases” (#ION-2017006) was approved by the Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Sciences.

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He, L., Zhou, Jh., Li, H. et al. Characterization of Gut Microbiota in Rats and Rhesus Monkeys After Methamphetamine Self-administration. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04318-x

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