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

Abstract

BackgroundEvidence 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 [11C](+)PHNO to compare receptor availability in groups with and without CD. MethodsTen 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. ResultsBPND 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. ConclusionsBetween-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.