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Microglia in neuroimmunopharmacology and drug addiction

Molecular Psychiatry (2024)Cite this article

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Abstract

Drug addiction is a chronic and debilitating disease that is considered a global health problem. Various cell types in the brain are involved in the progression of drug addiction. Recently, the xenobiotic hypothesis has been proposed, which frames substances of abuse as exogenous molecules that are responded to by the immune system as foreign “invaders”, thus triggering protective inflammatory responses. An emerging body of literature reveals that microglia, the primary resident immune cells in the brain, play an important role in the progression of addiction. Repeated cycles of drug administration cause a progressive, persistent induction of neuroinflammation by releasing microglial proinflammatory cytokines and their metabolic products. This contributes to drug addiction via modulation of neuronal function. In this review, we focus on the role of microglia in the etiology of drug addiction. Then, we discuss the dynamic states of microglia and the correlative and causal evidence linking microglia to drug addiction. Finally, possible mechanisms of how microglia sense drug-related stimuli and modulate the addiction state and how microglia-targeted anti-inflammation therapies affect addiction are reviewed. Understanding the role of microglia in drug addiction may help develop new treatment strategies to fight this devastating societal challenge.

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Fig. 1: Inflammation induced by psychostimulants.
Fig. 2: Microglial dynamics in the brain.
Fig. 3: TLR4 signaling contributes to drug addiction.

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Acknowledgements

This work was supported by STI2030-Major Projects [2021ZD0203000(2021ZD0203003)], the Beijing National Laboratory for Molecular Sciences (BNLMS202108), and the Chinese Academy of Sciences Pioneer Hundred Talents Program.

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Authors and Affiliations

  1. Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China

    Hongyuan Li & Xiaohui Wang

  2. Department of Psychology and Neuroscience, and the Center for Neuroscience, University of Colorado Boulder, Boulder, CO, 80309, USA

    Linda R. Watkins

  3. School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China

    Xiaohui Wang

  4. Beijing National Laboratory for Molecular Sciences, Beijing, 100190, China

    Xiaohui Wang

Authors
  1. Hongyuan Li
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  2. Linda R. Watkins
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  3. Xiaohui Wang
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Contributions

Hongyuan Li: organizational framework and construction, collected data, paper drafting; Linda R Watkins: revision and analysis; Xiaohui Wang: proposal, design and final revision.

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Correspondence to Xiaohui Wang.

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Li, H., Watkins, L.R. & Wang, X. Microglia in neuroimmunopharmacology and drug addiction. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02443-6

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