Ethanol-Associated Changes in Glutamate Reward Neurocircuitry

A Minireview of Clinical and Preclinical Genetic Findings

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

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

21 Citations (Scopus)

Abstract

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
PublisherElsevier
Pages41-85
Number of pages45
Volume137
ISBN (Print)9780128037867
DOIs
StatePublished - 2016

Publication series

NameProgress in Molecular Biology and Translational Science
Volume137
ISSN (Print)18771173
ISSN (Electronic)18780814

Fingerprint

Reward
Alcoholism
Glutamic Acid
Ethanol
Amino Acid Transport System X-AG
Gene Expression
Physiological Phenomena
Genetic Research
Genetic Models
Glutamate Receptors
Genetic Predisposition to Disease
Age of Onset
Neuroimaging
Neurotransmitter Agents
Proteins
Animal Models
Alcohols
Brain

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

Cite this

Bell, R., Hauser, S. R., McClintick, J., Rahman, S., Edenberg, H., Szumlinski, K. K., & McBride, W. J. (2016). Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings. In The Molecular Basis of Drug Addiction, 2016 (Vol. 137, pp. 41-85). (Progress in Molecular Biology and Translational Science; Vol. 137). Elsevier. https://doi.org/10.1016/bs.pmbts.2015.10.018

Ethanol-Associated Changes in Glutamate Reward Neurocircuitry : A Minireview of Clinical and Preclinical Genetic Findings. / Bell, Richard; Hauser, Sheketha R.; McClintick, Jeanette; Rahman, Shafiqur; Edenberg, Howard; Szumlinski, Karen K.; McBride, William J.

The Molecular Basis of Drug Addiction, 2016. Vol. 137 Elsevier, 2016. p. 41-85 (Progress in Molecular Biology and Translational Science; Vol. 137).

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

Bell, R, Hauser, SR, McClintick, J, Rahman, S, Edenberg, H, Szumlinski, KK & McBride, WJ 2016, Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings. in The Molecular Basis of Drug Addiction, 2016. vol. 137, Progress in Molecular Biology and Translational Science, vol. 137, Elsevier, pp. 41-85. https://doi.org/10.1016/bs.pmbts.2015.10.018
Bell R, Hauser SR, McClintick J, Rahman S, Edenberg H, Szumlinski KK et al. Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings. In The Molecular Basis of Drug Addiction, 2016. Vol. 137. Elsevier. 2016. p. 41-85. (Progress in Molecular Biology and Translational Science). https://doi.org/10.1016/bs.pmbts.2015.10.018
Bell, Richard ; Hauser, Sheketha R. ; McClintick, Jeanette ; Rahman, Shafiqur ; Edenberg, Howard ; Szumlinski, Karen K. ; McBride, William J. / Ethanol-Associated Changes in Glutamate Reward Neurocircuitry : A Minireview of Clinical and Preclinical Genetic Findings. The Molecular Basis of Drug Addiction, 2016. Vol. 137 Elsevier, 2016. pp. 41-85 (Progress in Molecular Biology and Translational Science).
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