D2R DNA transfer into the nucleus accumbens attenuates cocaine self-administration in rats
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Dopamine (DA) D2 receptor (D2R) agonists and antagonists can modulate self-administration behavior, conditioned place preference, and locomotor responses to cocaine. Low levels of D2R have also been observed in cocaine addicted subjects and in non human primates after chronic cocaine exposures. Prior studies had shown that D2R upregulation in the nucleus accumbens (NAc) in rodents trained to self-administer alcohol markedly attenuated alcohol preference and intake. Here we assess the effects of D2R upregulation in the NAc on cocaine intake in rats trained to self-administer cocaine. Following 2 weeks of i.v. cocaine self-administration (CSA), rats were stereotaxically treated with an adenovirus that carried the D2R gene to upregulate D2R in the NAc. D2R vector treatment resulted in a significant decrease (75%) in cocaine infusions and lever presses (70%) for cocaine. This effect lasted 6 days before cocaine consumption returned to baseline levels, which corresponds roughly to the time it takes D2R to return to baseline levels. These findings show that CSA and D2R in the NAc are negatively correlated and suggest that cocaine intake is modulated in part by D2R levels in NAc. Thus strategies aimed at increasing D2R expression in NAc may be beneficial in treating cocaine abuse and addiction.
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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., 2008
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., 2008
In the striatum, D2Rs mediate indirect pathway signalling to frontal cortical regions; their down-regulation enhances sensitization to drugs, whereas up-regulation interferes with drug consumption.
“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 [69]
In striatum, D2 receptors mediate indirect pathway signaling to frontocortical regions; down-regulation enhances drug sensitization, while upregulation interferes with drug consumption.
“In the striatum, D2 receptors mediate signaling through the indirect pathway that modulates frontocortical regions, and its down-regulation enhances drug sensitization in animal models (74), whereas its upregulation interferes with drug consumption (75).”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [75]
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Neurogenetics and gene therapy for reward deficiency syndrome: are we going to the Promised Land?
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D‐cycloserine facilitates extinction of cocaine self‐administration in c57 mice
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Self-citationEvidence for the DRD2 Gene as a Determinant of Reward Deficiency Syndrome (RDS).
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- Authors
- Thanos, P. K., Michaelides, M., Umegaki, H., & Volkow, N. D.
- Affiliations
- National Institutes of Health (US)
- Nagoya University (JP)
- Corresponding author
- Thanos, Panayotis K.
- Venue
- Synapse
- Publisher
- Wiley
- Published
- 2008-04-24
- Volume
- 62
- Issue
- 7
- Pages
- 481-486
- ISSN
- 0887-4476 (ISSN-L)
- 1098-2396
- PMC
- PMC2659016
- OpenAlex
- W2162366325
- Cited by
- 143
- References
- 43
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 13 · 2016: 13 · 2015: 13 · 2014: 8 · 2013: 12 · 2012: 12
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Synapse (publishedVersion, public-domain)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (AA-07611, R01AA011034, AA 07574, AA11034, Z01AA000551, P50AA007611, T32AA007574)
- 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 › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- dopamine D2 receptor, nucleus accumbens, cocaine self-administration, adenoviral gene transfer, cocaine dependence, cocaine addiction treatment
- MeSH terms
- Adenoviridae, Animals, Cocaine, DNA, Dopamine, Genetic Vectors, Male, Nucleus Accumbens, Reward, Self Administration, Up-Regulation, Treatment Outcome, Rats, Sprague-Dawley, Receptors, Dopamine D2, Gene Transfer Techniques, Dopamine Uptake Inhibitors, Cocaine-Related Disorders, Rats
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