The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index.
DRD2 Gene Transfer Into the Nucleus Accumbens Core of the Alcohol Preferring and Nonpreferring Rats Attenuates Alcohol Drinking
Abstract
BACKGROUND: Transient overexpression of the dopamine D2 receptor (DRD2) gene in the nucleus accumbens (NAc) using an adenoviral vector has been associated with a significant decrease in alcohol intake in Sprague Dawley rats. This overexpression of DRD2 reduced alcohol consumption in a two-bottle-choice paradigm and supported the view that high levels of DRD2 may be protective against alcohol abuse. METHODS: Using a limited access (1 hr) two-bottle-choice (water versus 10% ethanol) drinking paradigm, we examined the effects of the DRD2 vector in alcohol intake in the genetically inbred alcohol-preferring (P) and -nonpreferring (NP) rats. In addition, micro-positron emission tomography imaging was used at the completion of the study to assess in vivo the chronic (7 weeks) effects of ethanol exposure on DRD2 levels between the two groups. RESULTS: P rats that were treated with the DRD2 vector (in the NAc) significantly attenuated their alcohol preference (37% decrease) and intake (48% decrease), and these measures returned to pretreatment levels by day 20. A similar pattern of behavior (attenuation of ethanol drinking) was observed in NP rats. Analysis of the [C]raclopride micro-positron emission tomography data after chronic (7 weeks) exposure to ethanol revealed clear DRD2 binding differences between the P and NP rats. P rats showed 16% lower [C]raclopride specific binding in striatum than the NP rats. CONCLUSIONS: These findings further support our hypothesis that high levels of DRD2 are causally associated with a reduction in alcohol consumption and may serve as a protective factor against alcoholism. That this effect was seen in P rats, which are predisposed to alcohol intake, suggests that they are protective even in those who are genetically predisposed to high alcohol intake. It is noteworthy that increasing DRD2 significantly decreased alcohol intake but did not abolish it, suggesting that high DRD2 levels may specifically interfere with the administration of large quantities of alcohol. The significantly higher DRD2 concentration in NP than P rats after 7 weeks of ethanol therefore could account for low alcohol intake.
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“Notably, a similar manipulation results in decreased drug intake (Thanos et al., 2008; Thanos et al., 2005; Thanos et al., 2004; Thanos et al., 2001)”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Thanos et al., 2004
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Metadata
- Authors
- Thanos, P. K., Taintor, N. B., Rivera, S. N., Umegaki, H., Ikari, H., Roth, G., Ingram, D. K., Hitzemann, R., Fowler, J. S., Gatley, S. J., Wang, G., & Volkow, N. D.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Thanos, Panayotis K.
- Venue
- Alcoholism Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2004-05
- Volume
- 28
- Issue
- 5
- Pages
- 720-728
- ISSN
- 0145-6008 (ISSN-L)
- 1530-0277
- OpenAlex
- W2145340134
- Cited by
- 125
- References
- 76
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 1 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 10 · 2014: 6 · 2013: 9 · 2012: 7
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA-07611, R01AA011034, AA 07574, AA11034, T32AA007574)
- Indiana Alcohol Research Center
- 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, nucleus accumbens, alcohol preference, alcohol consumption, alcohol-preferring rats, alcohol-nonpreferring rats, adenoviral vector, genetic predisposition to alcoholism, chronic ethanol exposure, striatum, alcoholism prevention
- MeSH terms
- Alcohol Drinking, Ethanol, Animals, Male, Nucleus Accumbens, Self Administration, Species Specificity, Rats, Sprague-Dawley, Receptors, Dopamine D2, Gene Transfer Techniques, Rats
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