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Astrocytes in cocaine addiction and beyond

Molecular Psychiatry volume 27, pages 652–668 (2022)Cite this article

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Abstract

Drug addiction remains a key biomedical challenge facing current neuroscience research. In addition to neural mechanisms, the focus of the vast majority of studies to date, astrocytes have been increasingly recognized as an “accomplice.” According to the tripartite synapse model, astrocytes critically regulate nearby pre- and postsynaptic neuronal substrates to craft experience-dependent synaptic plasticity, including synapse formation and elimination. Astrocytes within brain regions that are implicated in drug addiction exhibit dynamic changes in activity upon exposure to cocaine and subsequently undergo adaptive changes themselves during chronic drug exposure. Recent results have identified several key astrocytic signaling pathways that are involved in cocaine-induced synaptic and circuit adaptations. In this review, we provide a brief overview of the role of astrocytes in regulating synaptic transmission and neuronal function, and discuss how cocaine influences these astrocyte-mediated mechanisms to induce persistent synaptic and circuit alterations that promote cocaine seeking and relapse. We also consider the therapeutic potential of targeting astrocytic substrates to ameliorate drug-induced neuroplasticity for behavioral benefits. While primarily focusing on cocaine-induced astrocytic responses, we also include brief discussion of other drugs of abuse where data are available.

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Fig. 1: Astrocyte-mediated regulation of transmission at the tripartite synapse.
Fig. 2: Dysregulation of NAc extracellular glutamate after cocaine experience.
Fig. 3: Astrocyte-mediated synaptogenesis after cocaine self-administration.

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Funding

Preparation of this review was supported by NIH grants R01DA014133 (EJN), R01DA040620 (EJN, YD), R21DA047861 (YD), R37DA023206 (YD), and R21DA051010 (YD).

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Authors and Affiliations

  1. Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA

    Junshi Wang, Susan R. Sesack & Yan Dong

  2. Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Junshi Wang, Leanne M. Holt & Eric J. Nestler

  3. Coriell Institute for Medical Research, Camden, NJ, USA

    Hugh H. Huang

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  1. Junshi Wang
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  2. Leanne M. Holt
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Correspondence to Eric J. Nestler or Yan Dong.

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Wang, J., Holt, L.M., Huang, H.H. et al. Astrocytes in cocaine addiction and beyond. Mol Psychiatry 27, 652–668 (2022). https://doi.org/10.1038/s41380-021-01080-7

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