Metabotropic Glutamate Receptors in Alcohol Use Disorder: Physiology, Plasticity, and Promising Pharmacotherapies

Max E. Joffe, Samuel W. Centanni, Anel A. Jaramillo, Danny G. Winder, P. Jeffrey Conn

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations


Developing efficacious treatments for alcohol use disorder (AUD) has proven difficult. The insidious nature of the disease necessitates a deep understanding of its underlying biology as well as innovative approaches to ameliorate ethanol-related pathophysiology. Excessive ethanol seeking and relapse are generated by long-term changes to membrane properties, synaptic physiology, and plasticity throughout the limbic system and associated brain structures. Each of these factors can be modulated by metabotropic glutamate (mGlu) receptors, a diverse set of G protein-coupled receptors highly expressed throughout the central nervous system. Here, we discuss how different components of the mGlu receptor family modulate neurotransmission in the limbic system and other brain regions involved in AUD etiology. We then describe how these processes are dysregulated following ethanol exposure and speculate about how mGlu receptor modulation might restore such pathophysiological changes. To that end, we detail the current understanding of the behavioral pharmacology of mGlu receptor-directed drug-like molecules in animal models of AUD. Together, this review highlights the prominent position of the mGlu receptor system in the pathophysiology of AUD and provides encouragement that several classes of mGlu receptor modulators may be translated as viable treatment options.

Original languageEnglish
Pages (from-to)2188-2204
Number of pages17
JournalACS Chemical Neuroscience
Issue number9
StatePublished - Sep 19 2018

Bibliographical note

Publisher Copyright:
© 2018 American Chemical Society.


  • Alcohol use disorder
  • bed nucleus of the stria terminalis
  • metabotropic glutamate receptor
  • nucleus accumbens
  • prefrontal cortex
  • synaptic plasticity

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology


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