Stimulant-induced dopamine increases are markedly blunted in active cocaine abusers
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Dopamine signaling in nucleus accumbens is essential for cocaine reward. Interestingly, imaging studies have reported blunted dopamine increases in striatum (assessed as reduced binding of [11C]raclopride to D2/D3 receptors) in detoxified cocaine abusers. Here, we evaluate whether the blunted dopamine response reflected the effects of detoxification and the lack of cocaine-cues during stimulant exposure. For this purpose we studied 62 participants (43 non-detoxified cocaine abusers and 19 controls) using positron emission tomography and [11C]raclopride (radioligand sensitive to endogenous dopamine) to measure dopamine increases induced by intravenous methylphenidate and in 24 of the cocaine abusers, we also compared dopamine increases when methylphenidate was administered concomitantly with a cocaine cue-video versus a neutral-video. In controls, methylphenidate increased dopamine in dorsal (effect size 1.4; P<0.001) and ventral striatum (location of accumbens) (effect size 0.89; P<0.001), but in cocaine abusers methylphenidate’s effects did not differ from placebo and were similar whether cocaine-cues were present or not. In cocaine abusers despite the markedly attenuated dopaminergic effects, the methylphenidate-induced changes in ventral striatum were associated with intense drug craving. Our findings are consistent with markedly reduced signaling through D2 receptors during intoxication in active cocaine abusers regardless of cues exposure, which might contribute to compulsive drug use.
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Conditioned cues in the incentive salience process appear to drive dopamine signalling to maintain drug-taking motivation even when pharmacological effects diminish.
“Conditioned cues within the incentive salience process appear to drive dopamine signalling to maintain motivation to take the drug, even when its pharmacological effects lessen.”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [61]
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Cocaine shifts dopamine D2 receptor sensitivity to gate conditioned behaviors
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PET radioligands for the dopamine D1-receptor: Application in psychiatric disorders
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Dopaminergic System Dysfunction in Recreational Dexamphetamine Users
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Striatal Dopamine D2/D3 Receptor Availability Varies Across Smoking Status
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Heteromerization of dopaminergic receptors in the brain: Pharmacological implications
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Expectation effects on brain dopamine responses to methylphenidate in cocaine use disorder
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Neural circuit selective for fast but not slow dopamine increases in drug reward
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Acute and Chronic Effects of Betel Quid Chewing on Brain Functional Connectivity
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Dürtüsellik ve Aşırı Yeme Arasındaki İlişki: Psikolojik ve Nörobiyolojik Yaklaşımlar
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Self-citation
- Authors
- Volkow, N. D., Tomasi, D., Wang, G.-J., Logan, J., Alexoff, D. L., Jayne, M., Fowler, J. S., Wong, C., Yin, P., & Du, C.
- Affiliations
- National Institute on Alcohol Abuse and Alcoholism (US)
- Brookhaven National Laboratory (US)
- Stony Brook University (US)
- Corresponding author
- Volkow, N D
- Venue
- Molecular Psychiatry
- Published
- 2014-06-10
- Volume
- 19
- Issue
- 9
- Pages
- 1037-1043
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC4827430
- OpenAlex
- W2162066549
- Semantic Scholar
- 0165ae458245252df7f8d918d2561a94276c11bc
- Cited by
- 134
- References
- 48
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 8 · 2023: 11 · 2022: 17 · 2021: 11 · 2020: 7 · 2019: 11 · 2018: 10 · 2017: 21 · 2016: 18 · 2015: 8 · 2014: 3
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (ZIAAA000550)
- 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 dependence, dopamine signaling, nucleus accumbens, striatum, D2/D3 receptors, cocaine cues, drug craving, compulsive drug use, cocaine detoxification
- MeSH terms
- Central Nervous System Stimulants, Brain, Brain Mapping, Cocaine, Cues, Dopamine, Humans, Male, Methylphenidate, Middle Aged, Video Recording, Visual Perception, Cohort Studies, Dopamine Uptake Inhibitors, Radiopharmaceuticals, Cocaine-Related Disorders, Raclopride, Positron-Emission Tomography, Craving
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