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

Abstract

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 [¹¹C]FLB 457 positron emission tomography and amphetamine to measure cortical D_2/3 receptors and dopamine release in CDSs.

Methods: [¹¹C]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 (BP_ND) and binding potential relative to total plasma concentration (BP_P) were derived using an arterial input function-based kinetic analysis. Cortical dopamine release in regions of interest was measured as the change in BP_ND and BP_P after amphetamine.

Results: Baseline D_2/3 receptor availability (BP_P and BP_ND) and amphetamine-induced dopamine release (ΔBP_ND and ΔBP_P) 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.