Cocaine Dependence and D2 Receptor Availability in the Functional Subdivisions of the Striatum: Relationship with Cocaine-Seeking Behavior

Martinez, Diana; Broft, Allegra; Foltin, Richard W; Slifstein, Mark; Hwang, Dah-Ren; Huang, Yiyun; Perez, Audrey; Frankel, W Gordon; Cooper, Thomas; Kleber, Herbert D; Fischman, Marian W; Laruelle, Marc

doi:10.1038/sj.npp.1300420

Cited by 306Neurotransmitter Receptor Influence on BehaviorSubstance Abuse Treatment and OutcomesNeural and Behavioral Psychology Studies

Cocaine Dependence and D2 Receptor Availability in the Functional Subdivisions of the Striatum: Relationship with Cocaine-Seeking Behavior

Martinez, Diana, Broft, Allegra, Foltin, Richard W, Slifstein, Mark, Hwang, Dah-Ren, Huang, Yiyun, Perez, Audrey, Frankel, W Gordon +4 more·2004·Neuropsychopharmacology

DOI 10.1038/sj.npp.1300420

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Abstract

Striatal dopamine D2 receptors have been implicated in the neurobiology of cocaine addiction. Previous imaging studies showed reduced striatal D2 receptor availability in chronic cocaine abusers, and animal studies suggested that low D2 receptor availability promotes cocaine self-administration. Here, D2 receptor availability was assessed with positron emission tomography (PET) and [11C]raclopride in the limbic, associative, and sensori-motor subdivisions of the striatum in 17 recently detoxified chronic cocaine-dependent (CCD) subjects and 17 matched healthy control (HC) subjects. In addition, the relationship between regional D2 receptor availability and behavioral measures obtained in cocaine self-administration sessions was investigated in CCD subjects. [11C]Raclopride binding potential was significantly reduced by 15.2% in the limbic striatum, 15.0% in the associative striatum, and 17.1% in the sensori-motor striatum in CCD subjects compared to HC subjects. In CCD subjects, no relationship was detected between D2 availability in striatal regions and either the positive effects of smoked cocaine or the choice of cocaine over an alternative reinforcer (money) following a priming dose of cocaine (a laboratory model of relapse). Thus, this study confirms previous reports of a modest decrease in D2 receptor availability in CCD subjects, and establishes that this decrease is generalized throughout the striatum. However, this study failed to demonstrate a relationship between D2 receptor availability and cocaine-induced cocaine-taking behavior. Additional research is warranted to unravel potential neurobiological traits that might confer vulnerability to relapse in detoxified CCD subjects.

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Cocaine dependence is associated with a decrease in D2 receptor binding, a pattern that seems to persist after disease remission.
“There are multiple lines of evidence that cocaine dependence is associated with a decrease in D2 receptor binding [164-167], a pattern that seems to persist after disease remission [165].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [164]
Cocaine abuse is associated with decreased D2 receptor availability in the striatum compared with controls, first reported in 1990 and confirmed by later studies.
“The first report was in 1990, where a study showed that cocaine abuse was associated with a decrease in D2 receptor availability in the striatum compared to controls (Volkow et al, 1990), and has been followed by a series of studies confirming this observation”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Martinez et al., 2004

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Self-citation

Dopamine D1 Receptors in Cocaine Dependence Measured with PET and the Choice to Self-Administer Cocaine
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Self-citation
Decreased striatal and enhanced thalamic dopaminergic responsivity in detoxified cocaine abusers
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Association of Low Striatal Dopamine D 2 Receptor Availability With Nicotine Dependence Similar to That Seen With Other Drugs of Abuse
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PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys
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PET Imaging of Dopamine D2 Receptor and Transporter Availability During Acquisition of Cocaine Self-administration in Rhesus Monkeys
Czoty, P. W., Gage, H. D., Nader, S. H., Reboussin, B. A., Bounds, M. C., & Nader, M. A. (2007) · Journal of Addiction Medicine · doi:10.1097/adm.0b013e318045c038 · Cited by 20 · see citing works

Authors: Martinez, D., Broft, A., Foltin, R. W., Slifstein, M., Hwang, D.-R., Huang, Y., Perez, A., Frankel, W. G., Cooper, T., Kleber, H. D., Fischman, M. W., & Laruelle, M.
Affiliations: Columbia University (US)
ORCID: Foltin, Richard W
Slifstein, Mark
Huang, Yiyun
Cooper, Thomas
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2004-03-10
Volume: 29
Issue: 6
Pages: 1190-1202
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/sj.npp.1300420
OpenAlex: W2088522292
Cited by: 306
References: 66
Citations by year: 2026: 6 · 2025: 8 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 10 · 2020: 31 · 2019: 10 · 2018: 8 · 2017: 14 · 2016: 20 · 2015: 7 · 2014: 21 · 2013: 25 · 2012: 31
FWCI: 3.75
Type: journal article
Language: en
Update notices: erratum (2004-08-23)
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Neuropsychopharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01da010219-06)
National Institute on Drug Abuse (2-R01-DA10219-01, PA50 DA 09236-06, K08 DA00483-01, P50DA009236, 09236)
National Center for Research Resources (M01RR000645, M01 RR00645)
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 D2 receptor, striatum, [11C]raclopride, limbic striatum, associative striatum, sensorimotor striatum, cocaine self-administration, cocaine-seeking behavior, relapse, addiction vulnerability
MeSH terms: Adult, Binding Sites, Brain Mapping, Choice Behavior, Cocaine, Corpus Striatum, Dose-Response Relationship, Drug, Female, Humans, Male, Self Administration, Time Factors, Tomography, Emission-Computed, Case-Control Studies, Receptors, Dopamine D2, Dopamine Antagonists, Dopamine Uptake Inhibitors, Cocaine-Related Disorders, Raclopride

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Cocaine Dependence and D2 Receptor Availability in the Functional Subdivisions of the Striatum: Relationship with Cocaine-Seeking Behavior

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