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 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.

• Authors: Rajesh Narendran, Neale Scott Mason, Michael L Himes, W Gordon Frankle
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 88 Issue 10 Pg. 788-796 (11 15 2020) ISSN: 1873-2402 [Electronic] United States
• PMID: 32507390 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Chemical References

• Pyrrolidines
• Salicylamides
• FLB 457
• Amphetamine
• Dopamine

Topics

• Amphetamine (pharmacology)
• Cocaine-Related Disorders (diagnostic imaging)
• Dopamine
• Humans
• Kinetics
• Positron-Emission Tomography
• Pyrrolidines
• Salicylamides