Dopaminergic network differences in human impulsivity

Science. 2010 Jul 30;329(5991):532. doi: 10.1126/science.1185778.

Abstract

Dopamine (DA) has long been implicated in impulsivity, but the precise mechanisms linking human variability in DA signaling to differences in impulsive traits remain largely unknown. By using a dual-scan positron emission tomography approach in healthy human volunteers with amphetamine and the D2/D3 ligand [18F]fallypride, we found that higher levels of trait impulsivity were predicted by diminished midbrain D2/D3 autoreceptor binding and greater amphetamine-induced DA release in the striatum, which was in turn associated with stimulant craving. Path analysis confirmed that the impact of decreased midbrain D2/D3 autoreceptor availability on trait impulsivity is mediated in part through its effect on stimulated striatal DA release.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Amphetamine-Related Disorders / etiology
  • Amphetamine-Related Disorders / metabolism
  • Autoreceptors / metabolism
  • Benzamides / metabolism
  • Corpus Striatum / metabolism*
  • Dextroamphetamine / administration & dosage*
  • Dopamine / metabolism*
  • Female
  • Humans
  • Impulsive Behavior / metabolism*
  • Ligands
  • Male
  • Positron-Emission Tomography
  • Pyrrolidines / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3 / metabolism*
  • Signal Transduction
  • Substantia Nigra / metabolism
  • Tegmentum Mesencephali / metabolism*
  • Ventral Tegmental Area / metabolism
  • Young Adult

Substances

  • Autoreceptors
  • Benzamides
  • Ligands
  • N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide
  • Pyrrolidines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Dextroamphetamine
  • Dopamine