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Synapse. 2011 Dec;65(12):1344-9. doi: 10.1002/syn.20970.

Imaging of dopamine D2/3 agonist binding in cocaine dependence: a [11C]NPA positron emission tomography study.

Author information

  • 1Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. narendranr@upmc.edu

Abstract

OBJECTIVE:

Positron emission tomography (PET) studies performed with [(11) C]raclopride have consistently reported lower binding to D(2/3) receptors and lower amphetamine-induced dopamine (DA) release in cocaine abusers relative to healthy controls. A limitation of these studies that were performed with D(2/3) antagonist radiotracers such as [(11) C]raclopride is the failure to provide information that is specific to D(2/3) receptors configured in a state of high affinity for the agonists (i.e., D(2/3) receptors coupled to G-proteins, D(2/3 HIGH) ). As the endogenous agonist DA binds with preference to D(2/3 HIGH) relative to D(2/3 LOW) receptors (i.e., D(2/3) receptors uncoupled to G-proteins) it is critical to understand the in vivo status of D(2/3 HIGH) receptors in cocaine dependence. Thus, we measured the available fraction of D(2/3) (HIGH) receptors in 10 recently abstinent cocaine abusers (CD) and matched healthy controls (HC) with the D(2/3) antagonist and agonist PET radiotracers [(11) C]raclopride and [(11) C]NPA.

METHODS:

[(11) C]raclopride and [(11) C]NPA binding potential (BP) (BP(ND) ) in the striatum were measured with kinetic analysis using the arterial input function. The available fraction of D(2/3 HIGH) receptors, i.e., % R(HIGH) available = D(2/3 HIGH) /(D(2/3 HIGH) + D(2/3 LOW) ) was then computed as the ratio of [(11) C]NPA BP(ND) /[(11) C]raclopride BP(ND) .

RESULTS:

No differences in striatal [(11) C]NPA BP(ND) (HC = 1.00 ± 0.17; CD = 0.97 ± 0.17, P = 0.67) or available % R(HIGH) (HC = 39% ± 5%; CD = 41% ± 5%, P = 0.50) was observed between cocaine abusers and matched controls.

CONCLUSIONS:

The results of this [(11) C]NPA PET study do not support alterations in D(2/3 HIGH) binding in the striatum in cocaine dependence.

Copyright © 2011 Wiley-Liss, Inc.

PMID:
21780185
[PubMed - indexed for MEDLINE]
PMCID:
PMC3419259
Free PMC Article
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