Cited by 65Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchSubstance Abuse Treatment and Outcomes

Ethanol-associated changes in glutamate reward neurocircuitry: a minireview of clinical and preclinical genetic findings

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Bell, Richard L., Hauser, Sheketha R., McClintick, Jeanette, Rahman, Shafiqur, Edenberg, Howard J., Szumlinski, Karen K., McBride, William J.·2016·Progress in molecular biology and translational science

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.

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  • SLC1A3 is a glutamate uptake transporter that plays important roles in the neurocircuitry of addiction.

    “Interestingly, the top DEG in astrocytes was AC008957.2, a lncRNA that is antisense to the gene encoding SLC1A3 , a glutamate uptake transporter that plays important roles in the neurocircuitry of addiction (38)(39)(40) .”

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  1. [84]Cozzoli DK Courson J Caruana AL Miller BW Thompson AB Wroten M Zhang PW Xiao B Hu J-H Klugmann M Metten P Worley PW Crabbe JC Szumlinski KK Accumbens shell metabotropic glutamate receptor 5-associated signaling regulates binge alcohol drinking: evidence from drinking-in-the-dark studies Alcohol Clin Exp Res 2012 36 1623 1633 22432643 PMC3382009
  2. [216]Gould AT Sacramento AD Wroten MG Miller BW Klugmann M Ben-Shahar O Szumlinski KK Extended access to intravenous cocaine imbalances ventromedial pre-frontal cortex Homer1 versus Homer2 expression: implications for relapse AddictBiol 2015 20 148 157 PMC3969898 24118426

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Authors
Bell, R. L., Hauser, S. R., McClintick, J., Rahman, S., Edenberg, H. J., Szumlinski, K. K., & McBride, W. J.
Affiliations
  • Indiana University School of Medicine (US)
  • Indiana University Indianapolis (US)
  • South Dakota State University (US)
  • University of California, Santa Barbara (US)
Corresponding author
Bell, Richard L.
Venue
Progress in molecular biology and translational science
Publisher
Elsevier
Published
2016
Volume
137
Pages
41-85
ISSN
1877-1173 (ISSN-L)
OpenAlex
W2416236000
Cited by
65
References
217
Citations by year
2026: 3 · 2025: 5 · 2024: 5 · 2023: 2 · 2022: 9 · 2021: 8 · 2020: 9 · 2019: 4 · 2018: 9 · 2017: 10 · 2016: 1
FWCI
19.17
Type
book chapter
Language
en
Open access
Locations
  • Progress in molecular biology and translational science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
Funders
National Institute on Alcohol Abuse and Alcoholism (U01AA013522, AA 13522, U24AA015512, R01AA016650, AA016650, R01AA020396, AA020396, U01AA016650, U24AA013522, U01AA020892, AA020892, P60AA007611)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
glutamate, alcoholism, ethanol, glutamate receptors, glutamate transporters, metabotropic glutamate receptors, ionotropic glutamate receptors, genetic predisposition to alcoholism, alcohol sensitivity, gene expression changes
MeSH terms
Ethanol, Animals, Brain, Humans, Glutamic Acid

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