title: Cortical dopamine release during a behavioral response inhibition task.
abstract: Dopamine (DA) dysregulation within fronto-striatal circuitry may underlie impulsivity in alcohol and other substance use disorders. To date, no one has directly demonstrated DA release during a task requiring the control of impulsive behavior. The current study was conducted to determine whether a response inhibition task (stop signal task; SST) would elicit detectable extrastriatal DA release in healthy controls. We hypothesized that DA release would be detected in regions previously implicated in different aspects of inhibitory control. [(18) F]Fallypride (FAL) PET imaging was performed in nine healthy males (24.6 ± 4.1 y.o.) to assess changes in cortical DA during a SST relative to a baseline "Go" task. On separate days, subjects received one FAL scan during the SST, and one FAL scan during a "Go" control; task-order was counter-balanced across subjects. Parametric BPND images were generated and analyzed with SPM8. Voxel-wise analysis indicated significant SST-induced DA release in several cortical regions involved in inhibitory control, including the insula, cingulate cortex, orbitofrontal cortex, precuneus, and supplementary motor area. There was a significant positive correlation between stop signal reaction time and DA release in the left orbitofrontal cortex, right middle frontal gyrus, and right precentral gyrus. These data support the feasibility of using FAL PET to study DA release during response inhibition, enabling investigation of relationships between DA function and impulsive behavior.
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, 46202; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, 46202.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Albrecht
authors.forename: David A
authors.initials: DA
authors.lastname: Kareken
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Christian
authors.forename: Mario
authors.initials: M
authors.lastname: Dzemidzic
authors.forename: Karmen K
authors.initials: KK
authors.lastname: Yoder
mesh_terms: D000328:Adult; D001549:Benzamides / Q000493:pharmacokinetics; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D056344:Executive Function / Q000502:physiology; D005240:Feasibility Studies; D006801:Humans; D007175:Impulsive Behavior / Q000378:metabolism; D007266:Inhibition, Psychological; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011759:Pyrrolidines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011930:Reaction Time; D013647:Task Performance and Analysis; D055815:Young Adult
chemical_list: D001549:Benzamides; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D004298:Dopamine
keywords: D2 receptor; dopamine; fallypride; impulsivity; positron emission tomography; stop signal task