Striatal Dopaminergic Abnormalities in Human Cocaine Users
Abstract
OBJECTIVE: Previous human postmortem experiments have shown an abnormally high number of dopamine uptake sites in the striatum of chronic cocaine users, which might contribute to cocaine withdrawal symptoms such as depression and suicidality. Previous inconsistencies in results were perhaps related to selective radioligand affinity changes or a coexisting loss of dopamine neurons. METHOD: In the present study, binding of the cocaine analog [3H]WIN 35428 to the dopamine transporter was assayed in postmortem striatal samples from 15 cocaine-using subjects and 15 matched comparison subjects to determine whether there were differences in number of binding sites or in affinity. Binding to the vesicular monoamine transporter, a measure of total dopaminergic terminals, was also assessed by using the radioligand (+)-[3H]dihydrotetrabenazine (DTBZ). RESULTS: Striatal [3H]WIN 35428 binding sites were significantly more numerous in the cocaine users: the mean Bmax value was 9.0 fmol bound/microg protein (SD = 2.8) for the cocaine users but only 6.0 (SD = 1.7) for the comparison subjects. Severity of chronic cocaine use was significantly related to [3H]WIN 35428 binding level. [3H]DTBZ binding was significantly lower in the cocaine users (mean = 330 nCi/mg, SD = 42) than in the comparison subjects (mean = 374, SD = 68). CONCLUSIONS: The present results confirm that cocaine users have a high number of dopamine transporter binding sites on dopaminergic neurons, despite an apparent low number of total dopamine terminals. These abnormalities may contribute to the abnormalities in subjective experience and behavior characteristic of chronic cocaine abusers.
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Increased DA-transporter expression has been shown in post-mortem analyses of brain tissue from human subjects addicted to cocaine.
“Increased DA-transporter expression has also been shown in post-mortem analyses of brain tissue from human subjects addicted to cocaine [75].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [75]
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- Authors
- Little, K. Y., Zhang, L., Desmond, T., Frey, K. A., Dalack, G. W., & Cassin, B. J.
- Affiliations
- University of Michigan (US)
- Venue
- American Journal of Psychiatry
- Published
- 1999-02-01
- Volume
- 156
- Issue
- 2
- Pages
- 238-245
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2118207252
- Cited by
- 116
- References
- 24
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 7 · 2013: 4 · 2012: 3
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01da009491-06)
- National Institute on Alcohol Abuse and Alcoholism (AA 07378, P50AA007378)
- National Institute on Aging (AG 08671, P50AG008671)
- National Institute on Drug Abuse (DA 09491)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- cocaine, striatum, dopamine transporter, dopamine uptake sites, vesicular monoamine transporter, dihydrotetrabenazine, postmortem brain, chronic cocaine use, cocaine withdrawal, dopaminergic neurons, dopaminergic terminals
- MeSH terms
- Adolescent, Adult, Autoradiography, Carrier Proteins, Cocaine, Corpus Striatum, Dopamine, Female, Humans, Male, Membrane Glycoproteins, Middle Aged, Nerve Tissue Proteins, Receptors, Dopamine, Severity of Illness Index, Tritium, Dopamine Uptake Inhibitors, Cocaine-Related Disorders, Membrane Transport Proteins, Dopamine Plasma Membrane Transport Proteins
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