Dopaminergic network differences in human impulsivity.
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.
Buckholtz
Joshua W
JW
Department of Psychology, Vanderbilt University, Nashville, TN 37240, USA. joshua.buckholtz@vanderbilt.edu
Treadway
Michael T
MT
Cowan
Ronald L
RL
Woodward
Neil D
ND
Li
Rui
R
Ansari
M Sib
MS
Baldwin
Ronald M
RM
Schwartzman
Ashley N
AN
Shelby
Evan S
ES
Smith
Clarence E
CE
Kessler
Robert M
RM
Zald
David H
DH
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
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