Striatal Dopamine D 2 /D 3 Receptor Availability Is Reduced in Methamphetamine Dependence and Is Linked to Impulsivity
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While methamphetamine addiction has been associated with both impulsivity and striatal dopamine D 2 /D 3 receptor deficits, human studies have not directly linked the latter two entities. We therefore compared methamphetamine-dependent and healthy control subjects using the Barratt Impulsiveness Scale (version 11, BIS-11) and positron emission tomography with [ 18 F]fallypride to measure striatal dopamine D 2 /D 3 receptor availability. The methamphetamine-dependent subjects reported recent use of the drug 3.3 g per week, and a history of using methamphetamine, on average, for 12.5 years. They had higher scores than healthy control subjects on all BIS-11 impulsiveness subscales ( p < 0.001). Volume-of-interest analysis found lower striatal D 2 /D 3 receptor availability in methamphetamine-dependent than in healthy control subjects ( p < 0.01) and a negative relationship between impulsiveness and striatal D 2 /D 3 receptor availability in the caudate nucleus and nucleus accumbens that reached statistical significance in methamphetamine-dependent subjects. Combining data from both groups, voxelwise analysis indicated that impulsiveness was related to D 2 /D 3 receptor availability in left caudate nucleus and right lateral putamen/claustrum ( p < 0.05, determined by threshold-free cluster enhancement). In separate group analyses, correlations involving the head and body of the caudate and the putamen of methamphetamine-dependent subjects and the lateral putamen/claustrum of control subjects were observed at a weaker threshold ( p < 0.12 corrected). The findings suggest that low striatal D 2 /D 3 receptor availability may mediate impulsive temperament and thereby influence addiction.
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Low striatal D2 receptor levels are associated with decreased baseline glucose metabolism in the prefrontal cortex, impulsivity in methamphetamine abusers, and compulsive cocaine administration in rodents.
“These low levels of striatal D2 receptors have been associated with decreases in baseline glucose metabolism (ie, a marker of brain function) in the prefrontal cortex (including dorsolateral prefrontal cortex, anterior cingulate gyrus, and medial orbitofrontal cortex),35,123,124 impulsivity in methamphetamine abusers,125 and compulsive cocaine administration in rodents.15”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [125]
Methamphetamine abuse is associated with lower D2 receptor binding compared with controls and higher impulsivity measured with the Barratt Impulsiveness Scale.
“Methamphetamine abuse is associated with lower D2 receptor binding compared to controls, and higher levels of impulsivity, measured with the Barratt Impulsiveness Scale (Lee et al., 2009).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Lee et al., 2009
Greater impulsivity in methamphetamine abusers correlates with lower D2 receptor binding in the caudate and nucleus accumbens.
“In addition, greater impulsivity in the methamphetamine abusers correlated with lower D2 receptor binding in the caudate and nucleus accumbens (Lee et al., 2009).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Lee et al., 2009
In methamphetamine abusers, low striatal D2R was associated with impulsivity.
“Indeed, in methamphetamine abusers, low striatal D2R was associated with impulsivity (Lee et al 2009), and it also predicted compulsive cocaine administration in rodents (Everitt et al 2008).”
From Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction (2011) · cites this paper as Lee et al 2009
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- Authors
- Lee, B., London, E. D., Poldrack, R. A., Farahi, J., Nacca, A., Monterosso, J. R., Mumford, J. A., Bokarius, A. V., Dahlbom, M., Mukherjee, J., Bilder, R. M., Brody, A. L., & Mandelkern, M. A.
- Affiliations
- University of California, Los Angeles (US)
- United States Department of Veterans Affairs (US)
- University of Southern California (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-11-25
- Volume
- 29
- Issue
- 47
- Pages
- 14734-14740
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2822639
- OpenAlex
- W2082078342
- Cited by
- 374
- References
- 58
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 10 · 2023: 12 · 2022: 23 · 2021: 14 · 2020: 26 · 2019: 15 · 2018: 18 · 2017: 29 · 2016: 28 · 2015: 27 · 2014: 34 · 2013: 40 · 2012: 36
- FWCI
- 10.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Marjorie M. Greene Trust
- National Institutes of Health
- University of California, Los Angeles (RL1DA024853)
- National Institute on Drug Abuse (RL1DA024853, R01DA020872, P20DA022539, R01DA020726)
- National Center for Research Resources ((M01 RR00865), M01RR000865)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- methamphetamine dependence, impulsivity, receptor availability, caudate nucleus, nucleus accumbens, claustrum, Barratt Impulsiveness Scale, addiction
- MeSH terms
- Adult, Basal Ganglia, Caudate Nucleus, Corpus Striatum, Dopamine, Female, Humans, Image Processing, Computer-Assisted, Impulsive Behavior, Functional Laterality, Male, Methamphetamine, Neuropsychological Tests, Nucleus Accumbens, Putamen, Biomarkers, Down-Regulation, Receptors, Dopamine D2, Dopamine Uptake Inhibitors, Amphetamine-Related Disorders, Positron-Emission Tomography, Receptors, Dopamine D3, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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