GABAA Receptors Containing ρ1 Subunits Contribute to In Vivo Effects of Ethanol in Mice
Open accessAbstract
GABAA receptors consisting of ρ1, ρ2, or ρ3 subunits in homo- or hetero-pentamers have been studied mainly in retina but are detected in many brain regions. Receptors formed from ρ1 are inhibited by low ethanol concentrations, and family-based association analyses have linked ρ subunit genes with alcohol dependence. We determined if genetic deletion of ρ1 in mice altered in vivo ethanol effects. Null mutant male mice showed reduced ethanol consumption and preference in a two-bottle choice test with no differences in preference for saccharin or quinine. Null mutant mice of both sexes demonstrated longer duration of ethanol-induced loss of righting reflex (LORR), and males were more sensitive to ethanol-induced motor sedation. In contrast, ρ1 null mice showed faster recovery from acute motor incoordination produced by ethanol. Null mutant females were less sensitive to ethanol-induced development of conditioned taste aversion. Measurement of mRNA levels in cerebellum showed that deletion of ρ1 did not change expression of ρ2, α2, or α6 GABAA receptor subunits. (S)-4-amino-cyclopent-1-enyl butylphosphinic acid ("ρ1" antagonist), when administered to wild type mice, mimicked the changes that ethanol induced in ρ1 null mice (LORR and rotarod tests), but the ρ1 antagonist did not produce these effects in ρ1 null mice. In contrast, (R)-4-amino-cyclopent-1-enyl butylphosphinic acid ("ρ2" antagonist) did not change ethanol actions in wild type but produced effects in mice lacking ρ1 that were opposite of the effects of deleting (or inhibiting) ρ1. These results suggest that ρ1 has a predominant role in two in vivo effects of ethanol, and a role for ρ2 may be revealed when ρ1 is deleted. We also found that ethanol produces similar inhibition of function of recombinant ρ1 and ρ2 receptors. These data indicate that ethanol action on GABAA receptors containing ρ1/ρ2 subunits may be important for specific effects of ethanol in vivo.
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ρ1 plays a central role in the in vivo behavioral effects of ethanol.
“In animal models, genetic deletion of ρ1 alters ethanol consumption, sensitivity, and motor effects, indicating that ρ1 plays a central role in the in vivo behavioral effects of ethanol.”
From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [71]
The Discussion reports that ρ1 deletion alters ethanol intake, sedation, and recovery from motor incoordination in mice. But the paper concludes that ρ1 is important for specific in vivo effects, and the Abstract describes a predominant role in two effects; calling its role central to ethanol’s in vivo behavioral effects more generally overstates that scope. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn animal models, genetic deletion of ρ1 alters ethanol consumption, sensitivity, and motor effects.
“In animal models, genetic deletion of ρ1 alters ethanol consumption, sensitivity, and motor effects, indicating that ρ1 plays a central role in the in vivo behavioral effects of ethanol.”
From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [71]
GABAA receptors containing ρ1, ρ2, or ρ3 subunits are expressed in multiple brain regions.
“The GABAA receptor family, particularly receptors containing ρ1, ρ2, or ρ3 subunits, has been primarily studied in retinal tissue but is also expressed in multiple brain regions.”
From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [71]
Receptors containing the ρ1 subunit are inhibited by low ethanol concentrations.
“Receptors containing the ρ1 subunit are inhibited by low ethanol concentrations.”
From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [71]
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- Authors
- Blednov, Y. A., Benavidez, J. M., Black, M., Leiter, C. R., Osterndorff-Kahanek, E., Johnson, D., Borghese, C. M., Hanrahan, J. R., Johnston, G. A. R., Chebib, M., & Harris, R. A.
- Affiliations
- The University of Texas at Austin (US)
- The University of Sydney (AU)
- Corresponding author
- Harris, R. Adron
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-01-16
- Volume
- 9
- Issue
- 1
- Pages
- e85525
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3894180
- OpenAlex
- W2135165474
- Cited by
- 60
- References
- 58
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 2 · 2017: 8 · 2016: 8 · 2015: 8 · 2014: 3
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Texas ScholarWorks (Texas Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (5r01aa006399-36, AA06399)
- National Institute on Alcohol Abuse and Alcoholism (R01-AA006399, R37AA006399, AA 06399, AA013520, U01AA013520)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- GABAA receptor, ethanol effects, ethanol consumption, ethanol preference, loss of righting reflex, ethanol-induced sedation, motor incoordination, conditioned taste aversion, sex differences, cerebellum, alcoholism
- MeSH terms
- Ethanol, Animals, Anxiety, Cells, Cultured, Central Nervous System Depressants, Female, gamma-Aminobutyric Acid, Ketamine, Male, Mice, Transgenic, Motor Activity, Phosphinic Acids, Receptors, GABA-A, Reflex, Startle, Xenopus laevis, GABA Agonists, Protein Subunits, Rotarod Performance Test, Mice, Reflex, Righting, GABA-A Receptor Antagonists
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