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Overexpression of dopamine D2 receptors reduces alcohol self‐administration
Abstract
The mechanism(s) underlying predisposition to alcohol abuse are poorly understood but may involve brain dopamine system(s). Here we used an adenoviral vector to deliver the dopamine D2 receptor (DRD2) gene into the nucleus accumbens of rats, previously trained to self‐administer alcohol, and to assess if DRD2 levels regulated alcohol preference and intake. We show that increases in DRD2 (52%) were associated with marked reductions in alcohol preference (43%), and alcohol intake (64%) of ethanol preferring rats, which recovered as the DRD2, returned to baseline levels. In addition, this DRD2 overexpression similarly produced significant reductions in ethanol non‐preferring rats, in both alcohol preference (16%) and alcohol intake (75%). This is the first evidence that overexpression of DRD2 reduces alcohol intake and suggests that high levels of DRD2 may be protective against alcohol abuse.
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“In the striatum, D2Rs mediate signalling in the striatal indirect pathway that modulates frontal cortical regions; and their down-regulation enhances sensitization to the effects of drugs in animal models (68), whereas their up-regulation interferes with drug consumption (69,70).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [70]
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Metadata
- Authors
- Thanos, P. K., Volkow, N. D., Freimuth, P., Umegaki, H., Ikari, H., Roth, G., Ingram, D. K., & Hitzemann, R.
- Affiliations
- Brookhaven National Laboratory (US)
- Pediatrics and Genetics (US)
- Nagoya University (JP)
- National Institute on Aging (US)
- Oregon Health & Science University (US)
- Corresponding author
- Thanos, Panayotis K.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2001-09
- Volume
- 78
- Issue
- 5
- Pages
- 1094-1103
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2141536473
- Cited by
- 324
- References
- 57
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 9 · 2023: 8 · 2022: 7 · 2021: 12 · 2020: 27 · 2019: 14 · 2018: 13 · 2017: 8 · 2016: 16 · 2015: 22 · 2014: 12 · 2013: 20 · 2012: 16
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Energy
- National Institute on Alcohol Abuse and Alcoholism (R01AA011034, AA 07574, AA11034, T32AA007574)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- dopamine D2 receptor, alcohol self-administration, alcohol preference, alcohol consumption, nucleus accumbens, dopaminergic system, adenoviral gene transfer
- MeSH terms
- Adenoviridae, Alcohol Drinking, Animals, Behavior, Animal, Brain Chemistry, Disease Models, Animal, Nucleus Accumbens, Self Administration, Genetic Therapy, Gene Expression, Rats, Sprague-Dawley, Receptors, Dopamine D2, Rats
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