Chronic Ethanol Administration Regulates the Expression of GABAA Receptor α1 and α5 Subunits in the Ventral Tegmental Area and Hippocampus
Abstract
Ethanol dependence and tolerance involve perturbation of GABAergic neurotransmission. Previous studies have demonstrated that ethanol treatment regulates the function and expression of GABAA receptors throughout the CNS. Conceivably, changes in receptor function may be associated with alterations of subunit composition. In the present study, a comprehensive (1-12 weeks) ethanol treatment paradigm was used to evaluate changes in GABAA receptor subunit expression in several brain regions including the cerebellum, cerebral cortex, ventral tegmental area (VTA) (a region implicated in drug reward/dependence), and the hippocampus (a region involved in memory/cognition). Expression of alpha 1 and alpha 5 subunits was regulated by ethanol in a region-specific and time-dependent manner. Following 2-4 weeks of administration, cortical and cerebellar alpha 1 and alpha 5 subunits immunoreactivity was reduced. In the VTA, levels of alpha 1 subunit immunoreactivity were significantly decreased after 12 weeks but not 1-4 weeks of treatment. Hippocampal alpha 1 subunit immunoreactivity and mRNA content were also significantly reduced after 12 but not after 4 weeks of treatment. In contrast, alpha 5 mRNA content was increased in this brain region. These data indicate that chronic ethanol administration alters GABAA receptor subunit expression in the VTA and hippocampus, effects that may play a role in the abuse potential and detrimental cognitive effects of alcohol.
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Long-term administration of ethanol reduces the expression of α1GABAARs in the VTA.
“For instance, long-term administration of ethanol reduces the expression of α1GABAARs in the VTA [117], possibly increasing baseline GABAergic inhibition over dopaminergic neurons and requiring higher ethanol concentrations for dopaminergic disinhibition.”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [117]
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- Authors
- Charlton, M. E., Sweetnam, P. M., Fitzgerald, L. W., Terwilliger, R. Z., Nestler, E. J., & Duman, R. S.
- Affiliations
- Yale University (US)
- DuPont (United States) (US)
- Corresponding author
- Charlton, Maura E.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1997-01
- Volume
- 68
- Issue
- 1
- Pages
- 121-127
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2064492505
- Cited by
- 109
- References
- 21
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 4 · 2021: 1 · 2020: 1 · 2019: 7 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 1 · 2014: 4 · 2013: 1 · 2012: 2
- FWCI
- 2.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Yale University
- National Institutes of Health (5r01da002297-18)
- National Institute on Drug Abuse (DA 08227, DA07359, DA 02297, P01DA008227)
- 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 › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- chronic ethanol exposure, GABAA receptor, alpha1 subunit, alpha5 subunit, ventral tegmental area, hippocampus, cerebellum, cerebral cortex, GABAergic neurotransmission, ethanol dependence, ethanol tolerance, alcohol abuse
- MeSH terms
- Ethanol, Animals, Cerebellum, Frontal Lobe, Hippocampus, Male, Parietal Lobe, RNA, Messenger, Tegmentum Mesencephali, Time Factors, Blotting, Western, Rats, Sprague-Dawley, Receptors, GABA, Rats, In Vitro Techniques
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