Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: effects on ethanol drinking
Open accessAbstract
Dopamine (DA) signals are transmitted via specific receptors including the D2 receptors (D2R). Previous studies have shown that D2R upregulation in the nucleus accumbens (NAc) attenuated alcohol consumption. We hypothesized that upregulation of D2R in the NAc would significantly influence alcohol drinking. We tested this hypothesis by determining the effect that D2R upregulation has on alcohol intake in genetically altered mice lacking D2Rs. After a steady baseline of drinking behavior was established for all mice, a null vector or a genetically modified adenoviral vector containing the rat D2R cDNA was infused into the NAc of wild-type (Drd2+/+), heterozygous (Drd2+/-), and receptor-deficient mice (Drd2-/-). Ethanol intake and preference were then determined using the two-bottle choice paradigm. Our results indicated that Drd2+/+ mice treated with the D2R vector significantly attenuated (58 %) their ethanol intake as well as reduced preference. Drd2+/- and mutant mice showed a similar attenuation, although the change was not as marked (12 %) and did not last as long. In contrast, Drd2-/- mice treated with the D2R vector displayed a temporary but significant increase (46 %) in ethanol intake and preference (consumption). These results supported the notion that the D2R plays an important role in alcohol consumption in mice and suggest that a key threshold range of D2R levels is associated with elevated alcohol consumption. Significant deviations in D2R levels from this range could impact alcohol consumption, and could help to explain possible individual variations in alcohol response, metabolism, sensitivity and consumption.
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Knock-down of D2 receptor in the striatum produces addiction-like compulsive eating in mice, whereas overexpression attenuates alcohol consumption and cocaine self-administration.
“Finally, knock-down of D2 receptor in the striatum produces addiction-like, compulsive eating in mice (Johnson and Kenny, 2010), whereas its overexpression attenuates alcohol consumption and cocaine self-administration (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., 2005
A similar manipulation to D2 receptor overexpression results in decreased drug intake.
“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., 2005
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References 44 · Cited by 108
- Authors
- Thanos, P. K., Rivera, S. N., Weaver, K., Grandy, D. K., Rubinstein, M., Umegaki, H., Wang, G. J., Hitzemann, R., & Volkow, N. D.
- Affiliations
- Brookhaven National Laboratory (US)
- Oregon Health & Science University (US)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Nagoya University (JP)
- Corresponding author
- Thanos, Panayotis K.
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 77
- Issue
- 2
- Pages
- 130-139
- ISSN
- 0024-3205 (ISSN-L)
- OpenAlex
- W2153532459
- Cited by
- 108
- References
- 44
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 6 · 2017: 1 · 2016: 9 · 2015: 8 · 2014: 7 · 2013: 10 · 2012: 5
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- Conicet (submittedVersion, cc-by-nc-sa)
- Funders
- U.S. Department of Energy (DEAC-02-98CH10886, -AC02-98 CH 10886, DE-AC02-)
- National Institute on Alcohol Abuse and Alcoholism (AA-07611, R01AA011034, AA 07574, AA11034, T32AA007574)
- National Institute of Mental Health (R01MH067497, MH67497, MH66360, R21MH066360)
- National Institute on Drug Abuse (DA-12062, R01DA012062)
- Brookhaven National Laboratory (AC-02-98CH10886, DE-AC02- 98CH10886)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- dopamine D2 receptor, ethanol consumption, alcohol preference, nucleus accumbens, adenoviral gene transfer, receptor up-regulation, alcohol consumption thresholds
- MeSH terms
- Alcohol Drinking, Animals, Conditioning, Psychological, Male, Mice, Inbred C57BL, Genetic Therapy, Receptors, Dopamine D2, Gene Transfer, Horizontal, Mice
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