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The Opioid-Addicted Tetrapartite Synapse

  • Author Footnotes
    1 AK and VCC contributed equally to this work.
    Anna Kruyer
    Footnotes
    1 AK and VCC contributed equally to this work.
    Affiliations
    Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina
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  • Author Footnotes
    1 AK and VCC contributed equally to this work.
    Vivian C. Chioma
    Footnotes
    1 AK and VCC contributed equally to this work.
    Affiliations
    Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina
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  • Peter W. Kalivas
    Correspondence
    Address correspondence to Peter W. Kalivas, Ph.D., 173 Ashley Avenue, MSC510, Charleston, SC 29425.
    Affiliations
    Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina
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  • Author Footnotes
    1 AK and VCC contributed equally to this work.

      Abstract

      Opioid administration in preclinical models induces long-lasting adaptations in reward and habit circuitry. The latest research demonstrates that in the nucleus accumbens, opioid-induced excitatory synaptic plasticity involves presynaptic and postsynaptic elements as well as adjacent astroglial processes and the perisynaptic extracellular matrix. We outline opioid-induced modifications within each component of the tetrapartite synapse and provide a neurobiological perspective on how these adaptations converge to produce addiction-related behaviors in rodent models. By incorporating changes observed at each of the excitatory synaptic compartments into a unified framework of opioid-induced glutamate dysregulation, we highlight new avenues for restoring synaptic homeostasis that might limit opioid craving and relapse vulnerability.

      Keywords

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