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