Alpha4 subunit‐containing GABAAreceptors in the accumbens shell contribute to the reinforcing effects of alcohol
Open accessAbstract
The α4βδ gamma-aminobutyric acid A receptor (GABA(A) R) has been proposed to mediate the rewarding effects of low-to-moderate concentrations of alcohol (ethanol) that approximate those achieved by social drinking. If this is true, then this receptor should be necessary for the reinforcing effects of ethanol as assessed in an instrumental self-administration procedure in which rats are trained to lever press for oral ethanol. We used viral-mediated RNA interference to transiently reduce expression of the α4 GABA(A) R subunit in the shell region of the nucleus accumbens (NAc). We found that responding for ethanol was significantly reduced after α4 reductions in the NAc shell, but not NAc core. This reduction was specific to ethanol, as responding for sucrose was not altered. The presence of ethanol was also required as unreinforced responding for ethanol in subjects previously trained to respond for ethanol (i.e. responding during an extinction test) was not altered. In addition, responding during reinforced sessions was not altered during the initial 5 minutes of the session, but decreased after 5 minutes, following multiple reinforced responses. Together, these findings indicate that the α4 GABA(A) R subunit in the NAc shell is necessary for the instrumental reinforcing effects of oral ethanol, further supporting a role for α4-containing GABA(A) Rs in the rewarding/reinforcing effects of ethanol. Possible pharmacological and non-pharmacological explanations for these effects are considered.
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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 [111]
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 [111]
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An emerging circuit pharmacology of GABAA receptors
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- Authors
- Rewal, M., Donahue, R., Gill, T. M., Nie, H., Ron, D., & Janak, P. H.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Janak, Patricia H.
- Venue
- Addiction Biology
- Publisher
- Wiley
- Published
- 2011-04-20
- Volume
- 17
- Issue
- 2
- Pages
- 309-321
- ISSN
- 1355-6215 (ISSN-L)
- 1369-1600
- PMC
- PMC3191302
- OpenAlex
- W2123693788
- Cited by
- 34
- References
- 56
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 6 · 2014: 8 · 2013: 2 · 2012: 3
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Addiction Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA016835)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- GABAA receptor subunits, nucleus accumbens shell, nucleus accumbens core, ethanol self-administration, alcohol reinforcement, alcohol reward, gene knockdown, sucrose self-administration, extinction
- MeSH terms
- Adenoviridae, Alcohol Drinking, Ethanol, Animals, Conditioning, Operant, Genetic Vectors, Male, Motor Activity, Psychomotor Performance, Receptors, GABA-A, Reinforcement, Psychology, Sucrose, Sweetening Agents, Rats, Long-Evans, RNA, Small Interfering, Rats, Gene Knockdown Techniques
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