α4-Containing GABA A Receptors in the Nucleus Accumbens Mediate Moderate Intake of Alcohol
Open accessAbstract
Alcohol has subjective and behavioral effects at the pharmacological levels typically reached during the consumption of one or two alcoholic drinks. Here we provide evidence that an alpha4-subunit-containing GABA(A) receptor contributes to the consumption of low-to-moderate levels of alcohol. Using viral-mediated RNA interference (RNAi), we found that reduced expression of the alpha4 subunit in the nucleus accumbens (NAc) shell of rats decreased their free consumption of and preference for alcohol. The time course for the reduced alcohol intake paralleled the time course of alpha4 mRNA reductions achieved after viral-mediated RNAi for alpha4. Furthermore, the reduction in drinking was region- and alcohol-specific: there was no effect of reductions in alpha4 expression in the NAc core on alcohol intake, and reductions in alpha4 expression in the NAc shell did not alter sucrose or water intake. These results indicate that the GABA(A) receptor alpha4 subunit in the NAc shell mediates alcohol intake.
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Ethanol modulation of high-sensitivity α4/6β3δ GABAARs may play an important role in the maintenance of ethanol self-administration.
“The ethanol modulation of these high-sensitivity receptors may play an important role in the maintenance of ethanol self-administration, as knockdown of α4GABAARs in the NAc shell (but not core) was sufficient to completely abolish self-administration of ethanol in rats [111, 112].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [112]
Knockdown of α4GABAARs in the NAc shell, but not core, completely abolishes self-administration of ethanol in rats.
“The ethanol modulation of these high-sensitivity receptors may play an important role in the maintenance of ethanol self-administration, as knockdown of α4GABAARs in the NAc shell (but not core) was sufficient to completely abolish self-administration of ethanol in rats [111, 112].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [112]
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An emerging circuit pharmacology of GABAA receptors
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- Authors
- Rewal, M., Jurd, R., Gill, T. M., He, D.-Y., Ron, D., & Janak, P. H.
- Affiliations
- University of California, San Francisco (US)
- Tufts University (US)
- Corresponding author
- Janak, Patricia H.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-01-14
- Volume
- 29
- Issue
- 2
- Pages
- 543-549
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2768359
- OpenAlex
- W2045771721
- Cited by
- 71
- References
- 51
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 2 · 2022: 1 · 2021: 7 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 3 · 2014: 10 · 2013: 4 · 2012: 9
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- University of California, San Francisco
- National Institute on Alcohol Abuse and Alcoholism (R01AA016835)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- nucleus accumbens shell, alcohol consumption, alcohol preference, alcohol regulation, sucrose intake
- MeSH terms
- Ethanol, Analysis of Variance, Animals, Cell Line, Transformed, Chromatography, Gas, Conditioning, Operant, Eating, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Humans, Male, Nucleus Accumbens, Receptors, GABA-A, RNA, Messenger, Time Factors, Transfection, Area Under Curve, Rats, Long-Evans, RNA, Small Interfering, Green Fluorescent Proteins, Rats
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