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.
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.
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