Imaging dopamine transmission in cocaine dependence: link between neurochemistry and response to treatment
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OBJECTIVE: Previous research has shown that dopamine signaling in the limbic striatum is crucial for selecting adaptive, motivated behavior and that disrupted dopamine transmission is associated with impulsive and maladaptive behavior. In humans, positron emission tomography (PET) imaging studies have shown that cocaine dependence is associated with the dysregulation of striatal dopamine signaling, which is linked to cocaine-seeking behavior. The goal of the present study was to investigate whether this association applies to the treatment setting. The authors hypothesized that dopamine signaling in the limbic striatum would be associated with response to a behavioral treatment that uses positive reinforcement to replace impulsive cocaine use with constructive personal goals. METHOD: Prior to treatment, cocaine-dependent subjects underwent two PET scans using [(11)C]raclopride, before and after the administration of a stimulant (methylphenidate), for measurement of striatal dopamine D(2/3) receptor binding and presynaptic dopamine release. RESULTS: Both of the outcome measures were lower in the volunteers who did not respond to treatment than in those who experienced a positive treatment response. CONCLUSIONS: These findings provide insight into the neurochemistry of treatment response and show that low dopamine transmission is associated with treatment failure. In addition, these data suggest that the combination of behavioral treatment with methods that increase striatal dopamine signaling might serve as a therapeutic strategy for cocaine dependence.
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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., 2011
In both studies, treatment responders did not differ from controls in measures of D2 receptor levels or dopamine release.
“Importantly, in both studies the subjects who responded to treatment did not differ from the control group in measures of D2 receptors levels or dopamine release.”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Martinez et al., 2011
Higher dopamine transmission and D2-dependent dopamine signaling in the nucleus accumbens are associated with greater willingness to work for larger but more effortful rewards.
“In other words, higher dopamine transmission and D2-dependent dopamine signaling in the nucleus accumbens are associated with greater willingness to work for larger but more effortful rewards, while lower dopamine and D2 receptor activity shifts animal’s choice towards less effortful and smaller immediate rewards (Figure 2).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Martinez et al., 2011
Treatment-seeking cocaine-dependent subjects with higher D2 receptor levels and higher dopamine release in the ventral striatum responded to contingency management treatment, while those with lower levels did not.
“The results showed that the cocaine-abusing subjects with higher D2 receptor levels and higher dopamine release in the ventral striatum responded to treatment, while those with lower levels did not (Martinez et al., 2011).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Martinez et al., 2011
In cocaine abusers, treatment responders had higher socioeconomic status than relapsers and did not differ from controls.
“the subjects who responded to treatment had a higher socioeconomic status compared to those who relapsed (Barratt Simplified Measure of Social Status: treatment responders 34.1 ± 9.2; non-responders 27.1 ± 4.5, p = 0.01), and actually did not differ from the control group (34.8 ± 7.9, p = 0.8).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Martinez et al., 2011
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- Authors
- Martinez, D., Carpenter, K. M., Liu, F., Slifstein, M., Broft, A., Friedman, A. C., Kumar, D., Van Heertum, R., Kleber, H. D., & Nunes, E.
- Affiliations
- From the Department of Psychiatry and the Department of Radiology, Columbia University College of Physicians and Surgeons, New York.
- Columbia University Irving Medical Center (US)
- Venue
- American Journal of Psychiatry
- Published
- 2011-06
- Volume
- 168
- Issue
- 6
- Pages
- 634-641
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC3235735
- OpenAlex
- W2166790971
- Cited by
- 212
- References
- 38
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 7 · 2023: 11 · 2022: 12 · 2021: 6 · 2020: 11 · 2019: 13 · 2018: 11 · 2017: 16 · 2016: 20 · 2015: 20 · 2014: 24 · 2013: 25 · 2012: 16
- FWCI
- 9.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (K24DA022412, K02DA026525, R01DA020855)
- National Center for Research Resources (UL1RR024156)
- 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, limbic striatum, presynaptic dopamine release, treatment response, behavior therapy, positive reinforcement, methylphenidate, cocaine-seeking behavior, impulsivity, treatment failure
- MeSH terms
- Adult, Central Nervous System Stimulants, Corpus Striatum, Dopamine, Female, Humans, Male, Methylphenidate, Neurochemistry, Case-Control Studies, Treatment Outcome, Receptors, Dopamine D2, Cocaine-Related Disorders, Positron-Emission Tomography
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