Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings

Richard L. Bell, Sheketha R. Hauser, Jeanette McClintick, Shafiqur Rahman, Howard J. Edenberg, Karen K. Szumlinski, William J. McBride

Research output: Chapter in Book/Report/Conference proceedingConference contribution

25 Scopus citations


Herein, we have reviewed the role of glutamate, the major excitatory neurotransmitter in the brain, in a number of neurochemical, -physiological, and -behavioral processes mediating the development of alcohol dependence. The findings discussed include results from both preclinical as well as neuroimaging and postmortem clinical studies. Expression levels for a number of glutamate-associated genes and/or proteins are modulated by alcohol abuse and dependence. These changes in expression include metabotropic receptors and ionotropic receptor subunits as well as different glutamate transporters. Moreover, these changes in gene expression parallel the pharmacologic manipulation of these same receptors and transporters. Some of these gene expression changes may have predated alcohol abuse and dependence because a number of glutamate-associated polymorphisms are related to a genetic predisposition to develop alcohol dependence. Other glutamate-associated polymorphisms are linked to age at the onset of alcohol-dependence and initial level of response/sensitivity to alcohol. Finally, findings of innate and/or ethanol-induced glutamate-associated gene expression differences/changes observed in a genetic animal model of alcoholism, the P rat, are summarized. Overall, the existing literature indicates that changes in glutamate receptors, transporters, enzymes, and scaffolding proteins are crucial for the development of alcohol dependence and there is a substantial genetic component to these effects. This indicates that continued research into the genetic underpinnings of these glutamate-associated effects will provide important novel molecular targets for treating alcohol abuse and dependence.

Original languageEnglish (US)
Title of host publicationThe Molecular Basis of Drug Addiction, 2016
EditorsShafiqur Rahman
PublisherElsevier B.V.
Number of pages45
ISBN (Print)9780128037867
StatePublished - Jan 1 2016

Publication series

NameProgress in Molecular Biology and Translational Science
ISSN (Print)1877-1173
ISSN (Electronic)1878-0814



  • addiction
  • alcohol nonpreferring
  • alcohol preferring
  • alcoholism
  • family history
  • genes and environment
  • genetics
  • glutamate system
  • pharmacogenetics
  • pharmacogenomics
  • predisposition
  • selective breeding

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Cite this

Bell, R. L., Hauser, S. R., McClintick, J., Rahman, S., Edenberg, H. J., Szumlinski, K. K., & McBride, W. J. (2016). Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings. In S. Rahman (Ed.), The Molecular Basis of Drug Addiction, 2016 (pp. 41-85). (Progress in Molecular Biology and Translational Science; Vol. 137). Elsevier B.V..