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

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

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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Oxazines
  • Receptors, Dopamine D3
  • naxagolide