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Abstract

Objective:

Positron emission tomography (PET) imaging studies in cocaine abusers have shown that low dopamine release in the striatum following an amphetamine challenge is associated with higher relapse rates. One possible mechanism that might lead to lower amphetamine-induced dopamine release is low availability of dopamine storage vesicles in the presynaptic terminals for release. Consistent with this hypothesis, postmortem studies have shown low levels of vesicular monoamine transporter, type 2 (VMAT2), the membrane protein that regulates the size of the vesicular dopamine pool, in cocaine abusers relative to healthy subjects. To confirm the postmortem findings, the authors used PET and the VMAT2 radioligand [11C]-(+)-dihydrotetrabenazine (DTBZ) to assess the in vivo VMAT2 availability in a group of 12 recently abstinent cocaine-dependent subjects and matched healthy comparison subjects.

Method:

[11C]DTBZ nondisplaceable binding potential (BPND) was measured by kinetic analysis using the arterial input function or, if arterial input was unavailable, by the simplified reference tissue method.

Results:

[11C]DTBZ BPND was significantly lower in the cocaine abusers than in the comparison subjects in the limbic striatum (10.0% lower), associative striatum (–13.4%), and sensorimotor striatum (–11.5%).

Conclusions:

The results of this in vivo PET study confirm previous in vitro reports of low VMAT2 availability in the striatum of cocaine abusers. It also suggests a compensatory down-regulation of the dopamine storage vesicles in response to chronic cocaine abuse and/or a loss of dopaminergic terminals. Further research is necessary to understand the clinical relevance of this observation to relapse and outcome in abstinent cocaine abusers.

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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: 55 - 63
PubMed: 22193525

History

Received: 23 January 2011
Revision received: 22 May 2011
Revision received: 11 July 2011
Accepted: 15 July 2011
Published online: 1 January 2012
Published in print: January 2012

Authors

Affiliations

Rajesh Narendran, M.D.
From the Departments of Radiology and Psychiatry, University of Pittsburgh; and the Department of Psychiatry, Columbia University Medical Center, New York.
Brian J. Lopresti, B.S.
From the Departments of Radiology and Psychiatry, University of Pittsburgh; and the Department of Psychiatry, Columbia University Medical Center, New York.
Diana Martinez, M.D.
From the Departments of Radiology and Psychiatry, University of Pittsburgh; and the Department of Psychiatry, Columbia University Medical Center, New York.
Neale Scott Mason, Ph.D.
From the Departments of Radiology and Psychiatry, University of Pittsburgh; and the Department of Psychiatry, Columbia University Medical Center, New York.
Michael Himes, B.S.
From the Departments of Radiology and Psychiatry, University of Pittsburgh; and the Department of Psychiatry, Columbia University Medical Center, New York.
Maureen A. May, B.S.
From the Departments of Radiology and Psychiatry, University of Pittsburgh; and the Department of Psychiatry, Columbia University Medical Center, New York.
Dennis C. Daley, Ph.D.
From the Departments of Radiology and Psychiatry, University of Pittsburgh; and the Department of Psychiatry, Columbia University Medical Center, New York.
Julie C. Price, Ph.D.
From the Departments of Radiology and Psychiatry, University of Pittsburgh; and the Department of Psychiatry, Columbia University Medical Center, New York.
Chester A. Mathis, Ph.D.
From the Departments of Radiology and Psychiatry, University of Pittsburgh; and the Department of Psychiatry, Columbia University Medical Center, New York.
W. Gordon Frankle, M.D.
From the Departments of Radiology and Psychiatry, University of Pittsburgh; and the Department of Psychiatry, Columbia University Medical Center, New York.

Notes

Address correspondence to Dr. Narendran ([email protected]).

Funding Information

Dr. Narendran's research group at the University of Pittsburgh has contractual research agreements with Sunovion and GlaxoSmithKline. Dr. Daley receives grant support from NIH/NIDA for research, receives royalties for written materials for professionals and individuals in recovery from several publishers (Oxford University Press; Hazelden Educational Materials; Daley Publications, and Independence Press), and receives royalties from Distance Learning for an online course based on his work. Dr. Mathis reports royalties from a license agreement between the University of Pittsburgh and GE Healthcare for amyloid imaging technology not related to this work; he has been a consultant for Elan, GE Healthcare, IBA, Janssen, and Wyeth/Pfizer. Dr. Frankle has been a consultant for Ono and Sunovion. The remaining authors report no financial relationships with commercial interests.Supported by award R03 DA-024704 from the National Institute on Drug Abuse (NIDA) under the American Reinvestment and Recovery Act of 2009 and by award CTSA-UL1 RR-024153 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIDA or the National Institutes of Health.

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