Amphetamine-induced dopamine release and neurocognitive function in treatment-naive adults with ADHD.

TitleAmphetamine-induced dopamine release and neurocognitive function in treatment-naive adults with ADHD.
Publication TypeJournal Article
Year of Publication2014
AuthorsCherkasova MV, Faridi N, Casey KF, O'Driscoll GA, Hechtman L, Joober R, Baker GB, Palmer J, Dagher A, Leyton M, Benkelfat C
JournalNeuropsychopharmacology
Volume39
Issue6
Pagination1498-507
Date Published2014 May
ISSN1740-634X
KeywordsAdult, Attention Deficit Disorder with Hyperactivity, Brain Mapping, Corpus Striatum, Dextroamphetamine, Dopamine, Dopamine Antagonists, Dopamine Uptake Inhibitors, Executive Function, Humans, Inhibition (Psychology), Male, Neuropsychological Tests, Psychiatric Status Rating Scales, Raclopride, Task Performance and Analysis
Abstract

Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [(11)C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87 ± 8.65) and 18 healthy male controls (age: 25.44 ± 6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [(11)C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [(11)C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.

DOI10.1038/npp.2013.349
Alternate JournalNeuropsychopharmacology
PubMed ID24378745
PubMed Central IDPMC3988554
Grant List77728 / / Canadian Institutes of Health Research / Canada