title: Dopaminergic network differences in human impulsivity.
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.
authors.affiliation: Department of Psychology, Vanderbilt University, Nashville, TN 37240, USA. joshua.buckholtz@vanderbilt.edu
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Buckholtz
authors.forename: Michael T
authors.initials: MT
authors.lastname: Treadway
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Cowan
authors.forename: Neil D
authors.initials: ND
authors.lastname: Woodward
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: M Sib
authors.initials: MS
authors.lastname: Ansari
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Schwartzman
authors.forename: Evan S
authors.initials: ES
authors.lastname: Shelby
authors.forename: Clarence E
authors.initials: CE
authors.lastname: Smith
authors.forename: Robert M
authors.initials: RM
authors.lastname: Kessler
authors.forename: David H
authors.initials: DH
authors.lastname: Zald
mesh_terms: D000293:Adolescent; D000328:Adult; D019969:Amphetamine-Related Disorders / Q000209:etiology / Q000378:metabolism; D017660:Autoreceptors / Q000378:metabolism; D001549:Benzamides / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D003913:Dextroamphetamine / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000378:metabolism*; D008024:Ligands; D008297:Male; D049268:Positron-Emission Tomography; D011759:Pyrrolidines / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D015398:Signal Transduction; D013378:Substantia Nigra / Q000378:metabolism; D013681:Tegmentum Mesencephali / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000378:metabolism; D055815:Young Adult
chemical_list: D017660:Autoreceptors; D001549:Benzamides; D008024:Ligands; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D003913:Dextroamphetamine; D004298:Dopamine