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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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
Cites
International Union of Pharmacology: Approaches to the Nomenclature of Voltage-Gated Ion Channels
Catterall, W. A., Chandy, K. G., Clapham, D. E., Gutman, G. A., Hofmann, F., Harmar, A. J., Abernethy, D. R., & Spedding, M. (2003) · Pharmacological Reviews · doi:10.1124/pr.55.4.5 · Cited by 7,126
Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors
Farrant, M., & Nusser, Z. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1625 · Cited by 2,081
Ethanol Inhibits NMDA-Activated Ion Current in Hippocampal Neurons
Lovinger, D. M., White, G., & Weight, F. F. (1989) · Science · doi:10.1126/science.2467382 · Cited by 1,448
Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology
Pritchett, D. B., Sontheimer, H. W., Shivers, B. D., Ymer, S., Kettenmann, H., Schofield, P. R., & Seeburg, P. H. (1989) · Nature · doi:10.1038/338582a0 · Cited by 1,273
Which GABAA-receptor subtypes really occur in the brain?
McKernan, R. M., & Whiting, P. J. (1996) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)80023-3 · Cited by 1,222
Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors
Mihic, S. J., Ye, Q., Wick, M. J., Koltchine, V. V., Krasowski, M. D., Finn, S. E., Mascia, M. P., Valenzuela, C. F., Hanson, K. K., Greenblatt, E. P., et al. (1997) · Nature · doi:10.1038/38738 · Cited by 1,219
Barnard, E. A., Skolnick, P., Olsen, R. W., Möhler, H., Sieghart, W., Biggio, G., Bræstrup, C., Bateson, A. N., & Langer, S. Z. (1998) · PubMed · Cited by 1,204
Benzodiazepine actions mediated by specific γ-aminobutyric acidA receptor subtypes
Rudolph, U., Crestani, F., Benke, D., Brünig, I., Benson, J. A., Fritschy, J.-M., Martin, J. R., Bluethmann, H., & Möhler, H. (1999) · Nature · doi:10.1038/44579 · Cited by 1,172
Nusser, Z., Sieghart, W., & Somogyi, P. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-05-01693.1998 · Cited by 835
Stell, B. M., Brickley, S. G., Tang, C., Farrant, M., & Módy, I. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2435457100 · Cited by 799
Flagged first, then by citations
2 of the 125 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Saxena, 1996, Properties of putative cerebellar GABAA receptor isoforms, Mol. Pharmacol., 49, 567
Cited by
Sorted by citations
Items 101–144 of 144
GABAA Receptors of Cerebellar Granule Cells in Culture: Interaction with Benzodiazepines
Cupello, A., Braccio, M. D., Gatta, E., Grossi, G., Nikas, P., Pellistri, F., & Robello, M. (2013) · Neurochemical Research · doi:10.1007/s11064-013-1171-4 · Cited by 7
GABAergic mechanisms in alcohol dependence
Uusi‐Oukari, M., & Korpi, E. R. (2024) · International review of neurobiology · doi:10.1016/bs.irn.2024.03.002 · Cited by 11
Discriminative stimulus effects of pregnanolone in rhesus monkeys
Gerak, L. R., & France, C. P. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3218-2 · Cited by 5
Neuronal Nicotinic Receptors in Sleep-Related Epilepsy: Studies in Integrative Biology
Becchetti, A. (2012) · ISRN Biochemistry · doi:10.5402/2012/262941 · Cited by 5
Turner, S. M. F., & Johnson, S. M. (2014) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2014.12.016 · Cited by 4
Use of Alcohol during Pregnancy in France: Another French Paradox?
Pierrefiche, O., & Daoust, M. (2016) · Journal of Pregnancy and Child Health · doi:10.4172/2376-127x.1000246 · Cited by 4
Introduction to Neuronal Networks of the Brain
Faingold, C. L., & Blumenfeld, H. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-415804-7.00001-0 · Cited by 4
Dépendance aux drogues : avancées de la neurobiologie et perspectives thérapeutiques
Marie, N., & Noble, F. (2012) · La Presse Médicale · doi:10.1016/j.lpm.2012.07.023 · Cited by 7
Vestal, B. E., Russell, P. H., Radcliffe, R. A., Bemis, L., Saba, L. M., & Kechris, K. J. (2018) · Brain and Behavior · doi:10.1002/brb3.989 · Cited by 3
On Some Physiological Aspects of Ethanol Repercussion on Neural and Cardiorenal Functions
Guedes, R. C. A., Paiva, A., dos Santos, Â. A., Filho, L. D. V., & Paixão, A. D. O. (2009) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/187152409789630433 · Cited by 3
Neuronal Network Effects of Drug Therapies for CNS Disorders
Faingold, C. L. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-415804-7.00032-0 · Cited by 3
Accelerometer-Based Alcohol Consumption Detection from Physical Activity
Kumar, D., Thanikkal, A., Krishnamurthy, P., Chen, X., & Zhang, P. (2021) · IEEE International Conference on Wireless and Mobile Computing, Networking and Communications (WiMob) · doi:10.1109/wimob52687.2021.9606257 · Cited by 2
Alcohol Modulation of Extra-synaptic Gamma-aminobutyric Acid Type A Receptors
Arslan, A. (2016) · Periodicals of Engineering and Natural Sciences (PEN) · doi:10.21533/pen.v4.i1.1809 · Cited by 2
Ethanol's Action Mechanisms in the Brain
Marin, M. T., & Morais‐Silva, G. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-805373-7.00016-5 · Cited by 2
Novel Targets for Drug Treatment in Psychiatry
Kurita, M., García‐Bea, A., & González‐Maeso, J. (2016) · Springer eBooks · doi:10.1007/978-1-4939-2528-5_30 · Cited by 1
Stuart, G. P., Hing, N., & Russell, A. M. T. (2022) · International Journal of Mental Health and Addiction · doi:10.1007/s11469-022-00849-3 · Cited by 1
Brain Alterations and Cognitive Deficits Induced by Alcohol Use Disorder
Naassïla, M. (2023) · Springer eBooks · doi:10.1007/978-3-031-32483-3_31 · Cited by 1
Dynamic Regulation of GABAA Receptor Biosynthesis and Transport
Bogdanov, Y. D. (2019) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-019-00810-3 · Cited by 1
Tobacco and Alcohol Use Behaviors
Hoft, N. R., Sakai, J. T., & Ehringer, M. A. (2010) · Issues in clinical child psychology · doi:10.1007/978-1-4419-5800-6_15 · Cited by 1
Characterizing specific henetic and environmental influences on alcohol use
Irons, D. E. (2012) · University of Minnesota Digital Conservancy (University of Minnesota)
Horn, L. A. (2012) · OhioLink ETD Center (Ohio Library and Information Network)
Otton, H. J., Janssen, A., & Wyllie, D. J. A. (2009) · Biochemical Society Transactions · doi:10.1042/bst0371423
GABA A receptor alpha 6 subunit
Siegel, R. E. (2008) · AfCS-Nature Molecule Pages · doi:10.1038/mp.a001003.01
Cognitive and synaptic dysfunction in a mouse model of Huntington's disease
Mitchell, R. C. (2012) · Discovery Research Portal (University of Dundee)
Molecular Organization of the Postsynaptic Membrane at Inhibitory Synapses
Arancibia‐Cárcamo, I. L., Triller, A., & Kittler, J. T. (2008) · Springer eBooks · doi:10.1007/978-0-387-77232-5_21
Reilly, W. J., Koirala, B., & Devaud, L. L. (2009)
Brundage, C. (2010) · ScholarWorks - UA (University of Alaska System) · doi:10.13140/rg.2.2.25294.31046
Glutamate and GABA signalling components in the human brain and in immune cells
Bhandage, A. K. (2016) · Uppsala University Publications (Uppsala University)
Mechanisms of ethanol-induced steroidogenesis following acute and chronic ethanol exposure
Boyd, K. N. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/begc-ks37
Ethanol Sensitivity and Tolerance of Rat Neuronal BK Channels: A Dissertation
Wynne, P. M. (2008) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/8ped-8a27
Extrasynaptic GABAA Receptors and Alcohol
Janak, P. H., & Long, V. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-405941-2.00013-4
Whissell, P. D. (2014) · TSpace (University of Toronto)
Gattás, D. (2018) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2018.tde-06042018-140935
Modulation of ventral periaqueductal gray dopamine neurons
Li, C. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/sk5m-2e97
The mechanisms of GABAergic signalling in the peripheral pain pathway
Ramli, R. B. (2019) · White Rose eTheses Online (University of Leeds, The University of Sheffield, University of York)
Lesmes, S. P. G. (2020) · Gredos (University of Salamanca) · doi:10.14201/gredos.145336
(2021) · Elsevier eBooks · doi:10.1016/b978-0-12-816793-9.00001-3
Kumar, D., Thanikkal, A., Krishnamurthy, P., Chen, X., & Zhang, P. (2022) · Advances in Science Technology and Engineering Systems Journal · doi:10.25046/aj070419
Neuroimaging in Drug and Substance Abuse
Morales, H., Fayed, N. M., & Fayed, A. (2024) · Springer eBooks · doi:10.1007/978-3-031-72219-6_44
Jönsson, S. (2012) · Gothenburg University Publications Electronic Archive (Gothenburg University)
BindingDB Entry 50017234: Clerodane Diterpenes from
BindingDB (2023) · UC San Diego · doi:10.7270/q2k64p33
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
