Dopamine D-3 receptor alterations in cocaine-dependent humans imaged with [C-11](+)PHNO

作者：Matuskey David^*; Gallezot Jean Dominique; Pittman Brian; Williams Wendol; Wanyiri Jane; Gaiser Edward; Lee Dianne E; Hannestad Jonas; Lim Keunpoong; Zheng Minq Qiang; Lin Shu fei; Labaree David; Potenza Marc N; Carson Richard E; Malison Robert T; Ding Yu Shin

来源：Drug and Alcohol Dependence, 2014, 139: 100-105.

DOI：10.1016/j.drugalcdep.2014.03.013

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

Background: Evidence from animal models and postmortem human studies points to the importance of the dopamine D-3 receptor (D3R) in cocaine dependence (CD). The objective of this pilot study was to use the D3R-preferring radioligand [C-11](+)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.

• 出版日期2014-6-1