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
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Research Support, N.I.H., Extramural
MeSH terms
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Adolescent
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Adult
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Amphetamine-Related Disorders / etiology
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Amphetamine-Related Disorders / metabolism
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Autoreceptors / metabolism
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Benzamides / metabolism
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Corpus Striatum / metabolism*
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Dextroamphetamine / administration & dosage*
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Dopamine / metabolism*
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Female
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Humans
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Impulsive Behavior / metabolism*
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Ligands
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Male
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Positron-Emission Tomography
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Pyrrolidines / metabolism
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Receptors, Dopamine D2 / metabolism
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Receptors, Dopamine D3 / metabolism*
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Signal Transduction
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Substantia Nigra / metabolism
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Tegmentum Mesencephali / metabolism*
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Ventral Tegmental Area / metabolism
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Young Adult
Substances
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Autoreceptors
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Benzamides
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Ligands
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N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide
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Pyrrolidines
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Receptors, Dopamine D2
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Receptors, Dopamine D3
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Dextroamphetamine
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Dopamine