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Signals from the Fourth Dimension Regulate Drug Relapse.

Patrick J Mulholland1, L Judson Chandler1, Peter W Kalivas2

  • 1Department of Neuroscience, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA; Department of Psychiatry and Behavioral Sciences, Addiction Sciences Division, Medical University of South Carolina, 67 President Street, Charleston, SC, 29425, USA.

Trends in Neurosciences
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PubMed
Summary

New insights into addiction treatment focus on the tetrapartite synapse, involving neurons, astroglia, and the extracellular matrix. Understanding these synaptic adaptations may lead to novel therapies for substance use disorders.

Keywords:
drug addictionextracellular matrixsynaptic plasticitytetrapartite synapses

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Area of Science:

  • Neuroscience
  • Addiction Research
  • Synaptic Plasticity

Background:

  • Substance use disorders (SUDs) pose a significant societal burden, yet effective treatments remain limited.
  • Existing research on drug-induced synaptic plasticity has not fully translated into successful addiction therapies.
  • Emerging evidence highlights the roles of astroglia and the extracellular matrix in synaptic plasticity.

Purpose of the Study:

  • To review constitutive corticostriatal adaptations shared across abused drugs from a tetrapartite synapse perspective.
  • To integrate recent findings on cell-type-specific neuronal adaptations in the striatum.
  • To explore how transient synaptic plasticity in drug-seeking behavior informs potential treatment strategies.

Main Methods:

  • Review of existing literature on corticostriatal adaptations and synaptic plasticity.
  • Integration of recent discoveries regarding cell type-specificity in striatal neurons.
  • Analysis of drug-seeking associated transient synaptic plasticity involving all four synaptic elements.

Main Results:

  • Abused drugs elicit shared constitutive corticostriatal adaptations involving the tetrapartite synapse.
  • Drug-seeking behavior is linked to transient synaptic plasticity requiring all four synaptic components.
  • Cell type-specific neuronal adaptations within the striatum are crucial in addiction.

Conclusions:

  • The tetrapartite synapse model offers a comprehensive framework for understanding addiction.
  • Targeting synaptic plasticity within the tetrapartite synapse presents promising avenues for novel addiction treatments.
  • Further research into astroglial and extracellular matrix roles in synaptic plasticity could revolutionize SUD therapy.