Addiction: Beyond dopamine reward circuitry
Open accessAbstract
Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction.
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Variants of PER2 are associated with D2 receptor availability and cocaine addiction vulnerability, risky alcohol drinking under high psychosocial stress, and disrupted sleep.
“Variants of PER2 are associated with D2 receptor availability and cocaine addiction vulnerability (133,134); risky alcohol drinking under high psychosocial stress (135); and disrupted sleep (136).”
From Impact of Sleep and Circadian Rhythms on Addiction Vulnerability in Adolescents (2018) · cites this paper as [134]
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- Authors
- Volkow, N. D., Wang, G.-J., Fowler, J. S., Tomasi, D., & Telang, F.
- Affiliations
- National Institutes of Health (US)
- Brookhaven National Laboratory (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-03-14
- Volume
- 108
- Issue
- 37
- Pages
- 15037-15042
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3174598
- OpenAlex
- W2020065445
- Cited by
- 959
- References
- 43
- Citations by year
- 2026: 63 · 2025: 78 · 2024: 51 · 2023: 53 · 2022: 56 · 2021: 87 · 2020: 58 · 2019: 45 · 2018: 60 · 2017: 69 · 2016: 75 · 2015: 78 · 2014: 75 · 2013: 50 · 2012: 47
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- addiction, dopamine, drug reward, nucleus accumbens, striatum, drug craving, dopamine D2 receptor, dopamine receptor binding, withdrawal, orbitofrontal cortex, anterior cingulate cortex, executive function, impulsivity, compulsive drug use
- MeSH terms
- Animals, Conditioning, Psychological, Dopamine, Humans, Models, Biological, Nerve Net, Reward, Behavior, Addictive
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.
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