Amphetamine-induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults With ADHD

Neuropsychopharmacology. 2014 May;39(6):1498-507. doi: 10.1038/npp.2013.349. Epub 2013 Dec 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / metabolism*
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Brain Mapping
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism*
  • Dextroamphetamine / blood
  • Dextroamphetamine / pharmacology*
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacokinetics
  • Dopamine Uptake Inhibitors / blood
  • Dopamine Uptake Inhibitors / pharmacology*
  • Executive Function / physiology
  • Humans
  • Inhibition, Psychological
  • Male
  • Neuropsychological Tests
  • Psychiatric Status Rating Scales
  • Raclopride / pharmacokinetics
  • Radionuclide Imaging
  • Task Performance and Analysis

Substances

  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • Raclopride
  • Dextroamphetamine
  • Dopamine