Imaging Cortical Dopamine Transmission In Cocaine Dependence: A [C-11]Flb 457-Amphetamine Positron Emission Tomography Study

BACKGROUND: Positron emission tomography studies have demonstrated less dopamine D-2/3 receptor availability and blunted psychostimulant-induced dopamine release in cocaine-dependent subjects (CDSs). No studies in CDSs have reported the in vivo status of D-2/3 and dopamine release in the cortex. Basic and functional imaging studies suggest a role for prefrontal cortical dopaminergic abnormalities in impaired executive function and relapse in cocaine dependence. We used [C-11]FLB 457 positron emission tomography and amphetamine to measure cortical D-2/3 receptors and dopamine release in CDSs.METHODS: [C-11]FLB 457 and positron emission tomography were used to measure D-2/3 receptor binding potential in cortical regions of interest in recently abstinent CDSs (n = 24) and healthy control subjects (n = 36) both before and after 0.5 mg kg(-1) of oral d-amphetamine. Binding potential relative to nondisplaceable uptake (BPND) and binding potential relative to total plasma concentration (BPP) were derived using an arterial input function-based kinetic analysis. Cortical dopamine release in regions of interest was measured as the change in BPND and BPP after amphetamine.RESULTS: Baseline D-2/3 receptor availability (BPP and BPND) and amphetamine-induced dopamine release (Delta BPND and Delta BPP) were significantly lower in the cortical regions in CDSs compared with healthy control subjects. Fewer D-2/3 receptors and less dopamine release in CDSs were not associated with performance on working memory and attention tasks.CONCLUSIONS: The results of this study suggest that deficits in dopamine D-2/3 transmission involve the cortex in cocaine dependence. Further studies to understand the clinical relevance of these findings are warranted.