Imaging Cortical Dopamine Transmission in Cocaine Dependence: A [11C]FLB 457–Amphetamine Positron Emission Tomography Study
| Autor: | Michael L. Himes, Rajesh Narendran, N.S. Mason, W. Gordon Frankle |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.diagnostic_test business.industry Working memory Dopaminergic Binding potential medicine.disease Cocaine dependence 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Endocrinology Positron emission tomography Dopamine Internal medicine Dopamine receptor D2 Medicine business Amphetamine 030217 neurology & neurosurgery Biological Psychiatry medicine.drug |
| Zdroj: | Biological Psychiatry. 88:788-796 |
| ISSN: | 0006-3223 |
| DOI: | 10.1016/j.biopsych.2020.04.001 |
| Popis: | Background Positron emission tomography studies have demonstrated less dopamine D2/3 receptor availability and blunted psychostimulant-induced dopamine release in cocaine-dependent subjects (CDSs). No studies in CDSs have reported the in vivo status of D2/3 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 D2/3 receptors and dopamine release in CDSs. Methods [11C]FLB 457 and positron emission tomography were used to measure D2/3 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 D2/3 receptor availability (BPP and BPND) and amphetamine-induced dopamine release (ΔBPND and ΔBPP) were significantly lower in the cortical regions in CDSs compared with healthy control subjects. Fewer D2/3 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 D2/3 transmission involve the cortex in cocaine dependence. Further studies to understand the clinical relevance of these findings are warranted. |
| Databáze: | OpenAIRE |
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