Ethanol-associated changes in glutamate reward neurocircuitry: a minireview of clinical and preclinical genetic findings
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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) .”
From Single cell transcriptome profiling of the human alcohol-dependent brain (2020) · cites this paper as [38]
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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.
- ORCID
- Venue
- Progress in molecular biology and translational science
- Publisher
- Elsevier
- Published
- 2016
- Volume
- 137
- Pages
- 41-85
- ISSN
- 1877-1173 (ISSN-L)
- PMC
- PMC4749142
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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