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Abstract

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 [11C]raclopride, before and after the administration of a stimulant (methylphenidate), for measurement of striatal dopamine D2/3 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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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 634 - 641
PubMed: 21406463

History

Received: 21 May 2010
Revision received: 2 September 2010
Revision received: 27 October 2010
Revision received: 9 December 2010
Accepted: 13 December 2010
Published online: 1 June 2011
Published in print: June 2011

Authors

Details

Diana Martinez, M.D.
From the Department of Psychiatry and the Department of Radiology, Columbia University College of Physicians and Surgeons, New York.
Kenneth M. Carpenter, Ph.D.
From the Department of Psychiatry and the Department of Radiology, Columbia University College of Physicians and Surgeons, New York.
Fei Liu, Ph.D.
From the Department of Psychiatry and the Department of Radiology, Columbia University College of Physicians and Surgeons, New York.
Mark Slifstein, Ph.D.
From the Department of Psychiatry and the Department of Radiology, Columbia University College of Physicians and Surgeons, New York.
Allegra Broft, M.D.
From the Department of Psychiatry and the Department of Radiology, Columbia University College of Physicians and Surgeons, New York.
Alessandra Calvo Friedman, B.A.
From the Department of Psychiatry and the Department of Radiology, Columbia University College of Physicians and Surgeons, New York.
Dileep Kumar, Ph.D.
From the Department of Psychiatry and the Department of Radiology, Columbia University College of Physicians and Surgeons, New York.
Ronald Van Heertum, M.D.
From the Department of Psychiatry and the Department of Radiology, Columbia University College of Physicians and Surgeons, New York.
Herbert D. Kleber, M.D.
From the Department of Psychiatry and the Department of Radiology, Columbia University College of Physicians and Surgeons, New York.
Edward Nunes, M.D.
From the Department of Psychiatry and the Department of Radiology, Columbia University College of Physicians and Surgeons, New York.

Notes

Address correspondence and reprint requests to Dr. Martinez, New York State Psychiatric Institute, Box 31, 1051 Riverside Dr., New York, NY 10032; [email protected] (e-mail).

Funding Information

Dr. Slifstein has consulted for GlaxoSmithKline and Amgen and has received research support from IntraCellular Therapies and Pierre-Fabre within the past 36 months. Dr. Kleber reports financial relationships with the Grunenthal Group, Purdue Pharmaceutical, Ascend Media, Neuromed, TEVA, Reckitt Benckiser, Alkermes, Abbott, Johnson & Johnson, and US WorldMeds. Dr. Nunes has received funding from the National Institute on Drug Abuse. The remaining authors report no financial relationships with commercial interests.Supported by National Institute on Drug Abuse grants R01 DA-020855, K02 DA-026525, and K24 DA-022412 and by grant UL1 RR-024156-03 from the NIH Division of Research Resources.

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