Dopamine D₃ receptor alterations in cocaine-dependent humans imaged with [¹¹C](+)PHNO.

Abstract

BACKGROUND:

Evidence from animal models and postmortem human studies points to the importance of the dopamine D₃ receptor (D₃R) in cocaine dependence (CD). The objective of this pilot study was to use the D₃R-preferring radioligand [(11)C](+)PHNO to compare receptor availability in groups with and without CD.

METHODS:

Ten medically healthy, non-treatment seeking CD subjects (mean age 41 ± 8) in early abstinence were compared to 10 healthy control (HC) subjects (mean age 41 ± 6) with no history of cocaine or illicit substance abuse. Binding potential (BPND), a measure of available receptors, was determined with parametric images, computed using the simplified reference tissue model (SRTM2) with the cerebellum as the reference region.

RESULTS:

BPND in CD subjects was higher in D₃R-rich areas including the substantia nigra ((SN) 29%; P=0.03), hypothalamus (28%; P=0.02) and amygdala (35%; P=0.03). No between-group differences were observed in the striatum or pallidum. BPND values in the SN (r=+0.83; P=0.008) and pallidum (r=+0.67; P=0.03) correlated with years of cocaine use.

CONCLUSIONS:

Between-group differences suggest an important role for dopaminergic transmission in the SN, hypothalamus and amygdala in CD. Such findings also highlight the potential relevance of D₃R as a medication development target in CD.

• Authors: David Matuskey, Jean-Dominique Gallezot, Brian Pittman, Wendol Williams, Jane Wanyiri, Edward Gaiser, Dianne E Lee, Jonas Hannestad, Keunpoong Lim, Minq-Qiang Zheng, Shu-fei Lin, David Labaree, Marc N Potenza, Richard E Carson, Robert T Malison, Yu-Shin Ding
• Journal: Drug and alcohol dependence (Drug Alcohol Depend) Vol. 139 Pg. 100-5 (Jun 01 2014) ISSN: 1879-0046 [Electronic] Ireland
• PMID: 24717909 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Oxazines
• Receptors, Dopamine D3
• naxagolide

Topics

• Adult
• Brain (diagnostic imaging, drug effects, metabolism, pathology)
• Case-Control Studies
• Cocaine-Related Disorders (diagnostic imaging, metabolism, pathology)
• Female
• Globus Pallidus (diagnostic imaging, drug effects, metabolism)
• Humans
• Male
• Neuroimaging
• Oxazines
• Positron-Emission Tomography (methods)
• Receptors, Dopamine D3 (metabolism)
• Substantia Nigra (diagnostic imaging, drug effects, metabolism)