Imaging studies on the role of dopamine in cocaine reinforcement and addiction in humans
Abstract
We summarize our studies with positron emission tomography investigating the role of dopamine (DA) in the reinforcing effects of cocaine and methylphenidate in humans and its involvement in cocaine addiction. These studies have shown that the rate at which cocaine and methylphenidate enter the brain and block the dopamine transporters (DAT) is the variable associated with the 'high', rather than the presence per se of the drug in the brain. Our studies also show that, while the level of DAT blockade is important in predicting the intensity of the 'high' induced by these drugs (DAT blockade > 50% is required for these drugs to induce a 'high'), the rate at which DAT are blocked determines whether the 'high' is perceived or not. Thus, oral methylphenidate, which leads to slow DAT blockade, does not induce a 'high', even at doses which block DAT more than 60%. In cocaine abusers, we have shown significant reductions in DA D2 receptors that are associated with decreased metabolism in cingulate gyrus and in orbitofrontal cortex. We suggest that this is one of the mechanisms by which DA disruption leads to compulsive drug administration in cocaine addiction. Cocaine abusers also show significant decreases in DA release, which coupled with the reduction in D2 receptors may result in decreased activation of reward circuits by physiological reinforcers and may perpetuate cocaine use as a means to compensate for this deficit. Thus, strategies to enhance DA brain function in ways that mimic physiological DA activity may be of help in overcoming cocaine addiction.
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The greater the positive velocity in dopamine receptor binding in the ventral striatum induced by psychomotor stimulants, the greater the subjective effect of high.
“As mentioned above, the greater the positive velocity in dopamine receptor binding in the ventral striatum induced by the administration of psychomotor stimulants, the greater the subjective effect of “high” (Volkow et al., 1999; 2002).”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Volkow et al., 1999
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- Authors
- Volkow, N. D., Fowler, J. S., & Wang, G.-J.
- Affiliations
- Brookhaven National Laboratory (US)
- Corresponding author
- Volkow, Nora D.
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 1999-07
- Volume
- 13
- Issue
- 4
- Pages
- 337-345
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W2056878909
- Cited by
- 315
- References
- 64
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 11 · 2022: 7 · 2021: 12 · 2020: 9 · 2019: 8 · 2018: 5 · 2017: 7 · 2016: 10 · 2015: 10 · 2014: 8 · 2013: 16 · 2012: 18
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01da009490-08)
- National Institute on Drug Abuse (DA-06891, DA-09490, DA-06278, R01DA006278, R01DA006891)
- 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 › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- cocaine, dopamine, cocaine dependence, methylphenidate, drug reinforcement, dopamine D2 receptor, cingulate gyrus, orbitofrontal cortex, dopamine release, reward systems, compulsive drug use, positron emission tomography
- MeSH terms
- Animals, Brain, Carrier Proteins, Cocaine, Dopamine, Humans, Membrane Glycoproteins, Nerve Tissue Proteins, Receptors, Dopamine, Reinforcement, Psychology, Tomography, Emission-Computed, Cocaine-Related Disorders, Membrane Transport Proteins, Dopamine Plasma Membrane Transport Proteins
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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