The DOI matches its Crossref record; 123 of the 125 references it cites were found in a registry or an index.
GABAA receptor subtypes: the ‘one glass of wine’ receptors
Open accessAbstract
This review discusses evidence for and apparent controversy about, gamma-aminobutyric acid type A (GABAA) receptor (GABAAR) subtypes that mediate alcohol effects experienced during social drinking. GABAARs that contain the beta3 and delta subunits were shown to be enhanced by alcohol concentrations that mirror the concentration dependence of alcohol responses in humans. A mutation (alpha6R100Q) previously found in alcohol nontolerant rats in the cerebellar GABAAR alpha6 subunit is sufficient for increased alcohol-induced ataxia in rats homozygous for this mutation (alpha6-100QQ) and further increases alcohol sensitivity of tonic GABA currents (mediated by alpha6betadelta receptors) in cerebellar granule cells of alpha6-100QQ rats and in recombinant alpha6R100Qbeta3delta receptors. This provided the first direct evidence that these types of receptors mediate behavioral effects of ethanol. Furthermore, the behavioral alcohol antagonist Ro15-4513 specifically reverses ethanol enhancement on alpha4/6beta3delta receptors. Unexpectedly, native and recombinant alpha4/6beta3delta receptors bind the behavioral alcohol antagonist Ro15-4513 with high affinity and this binding is competitive with EtOH, suggesting a specific and mutually exclusive (competitive) ethanol/Ro15-4513 site, which explains the puzzling activity of Ro15-4513 as a behavioral alcohol antagonist. Our conclusion from these findings is that alcohol/Ro15-4513-sensitive GABAAR subtypes are important alcohol targets and that alcohol at relevant concentrations is more specific than previously thought. In this review, we discuss technical difficulties in expressing recombinant delta subunit-containing receptors in oocytes and mammalian cells that may have contributed to negative results and confusion. Not only because we have reproduced detailed positive results numerous times, and we and many others have built extensively on basic findings, but also because we explain and combine many previously puzzling results into a coherent and highly plausible paradigm on how alcohol exerts an important part of its action in the brain, we are confident about our findings and conclusions. However, many important open questions remain to be answered.
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In the citing paper
“Another GABAAR-modulating drug of abuse, ethanol, at high doses potentiates GABA-gated current in a mostly nonselective manner in terms of the GABAAR subunits, with the exception of the α4/6β3δ GABAARs, which seem to be sensitive to low concentrations of ethanol as observed with social drinking [110].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [110]
In the citing paper
“Another GABAAR-modulating drug of abuse, ethanol, at high doses potentiates GABA-gated current in a mostly nonselective manner in terms of the GABAAR subunits, with the exception of the α4/6β3δ GABAARs, which seem to be sensitive to low concentrations of ethanol as observed with social drinking [110].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [110]
In the citing paper
“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 [110]
Citations
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Sorted by citations
Olsen, R. W., & Sieghart, W. (2008) · Pharmacological Reviews · doi:10.1124/pr.108.00505 · Cited by 1,064
A DNA methylation biomarker of alcohol consumption
Liu, C., Marioni, R. E., Hedman, Å. K., Pfeiffer, L., Tsai, P.-C., Reynolds, L. M., Just, A. C., Duan, Q., Boer, C. G., Tanaka, T., et al. (2018) · Molecular Psychiatry · doi:10.1038/mp.2016.192 · Cited by 402
GABAA receptor: Positive and negative allosteric modulators
Olsen, R. W. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.01.036 · Cited by 369
The role of GABAA receptors in the development of alcoholism
Enoch, M. (2008) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2008.03.007 · Cited by 243
GABA tone regulation and its cognitive functions in the brain
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Metadata
- Authors
- Olsen, R. W., Hanchar, H. J., Meera, P., & Wallner, M.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Wallner, Martin
- Venue
- Alcohol
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 41
- Issue
- 3
- Pages
- 201-209
- ISSN
- 0741-8329 (ISSN-L)
- PMC
- PMC2852584
- OpenAlex
- W1978493649
- Cited by
- 142
- References
- 125
- Citations by year
- 2024: 4 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 2 · 2019: 9 · 2018: 11 · 2017: 7 · 2016: 8 · 2015: 7 · 2014: 16 · 2013: 6 · 2012: 15
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcohol (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (F31AA015460, AA 015460, AA07680, R37AA007680, R01AA007680)
- National Institute of Neurological Disorders and Stroke (NS-35985, P01NS035985)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- GABAA receptor subtypes, alcohol effects, social drinking, alpha6 subunit, cerebellar granule cells, Ro 15-4513, alcohol sensitivity
- MeSH terms
- Ethanol, Animals, Azides, Benzodiazepines, Central Nervous System Depressants, Humans, Receptors, GABA-A, Wine
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