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Drug Alcohol Depend. 2014 Jun 1;139:100-5. doi: 10.1016/j.drugalcdep.2014.03.013. Epub 2014 Mar 20.

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

Author information

  • 1Department of Psychiatry, Yale University, New Haven, CT, USA; Department of Diagnostic Radiology, Yale University, New Haven, CT, USA. Electronic address: david.matuskey@yale.edu.
  • 2Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
  • 3Department of Psychiatry, Yale University, New Haven, CT, USA.
  • 4Department of Psychiatry, Yale University, New Haven, CT, USA; Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
  • 5Department of Radiology and Psychiatry, New York University School of Medicine, New York, NY, USA.

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.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS:

Cocaine; D(3); Dopamine; Human; PET; [(11)C](+)PHNO

PMID:
24717909
[PubMed - indexed for MEDLINE]
PMCID:
PMC4071607
[Available on 2015-06-01]
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