Dopaminergic Network Differences in Human Impulsivity

• Published in: Science (American Association for the Advancement of Science) Vol. 329; no. 5991; p. 532
• Main Authors: Buckholtz, Joshua W, Treadway, Michael T, Cowan, Ronald L, Woodward, Neil D, Li, Rui, Ansari, M. Sib, Baldwin, Ronald M, Schwartzman, Ashley N, Shelby, Evan S, Smith, Clarence E, Kessler, Robert M, Zald, David H
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 30-07-2010; The American Association for the Advancement of Science
• Subjects: Adolescent; Adult; Amphetamine-Related Disorders - etiology; Amphetamine-Related Disorders - metabolism; Amphetamines; Autoreceptors; Autoreceptors - metabolism; Availability; Benzamides - metabolism; Binding; Binding sites; Biological and medical sciences; BREVIA; Corpus Striatum - metabolism; Dextroamphetamine - administration & dosage; Dopamine; Dopamine - metabolism; Female; Fundamental and applied biological sciences. Psychology; Human; Humans; Impulsive Behavior - metabolism; Impulsiveness; Joining; Ligands; Male; Midbrain; Neuropsychology; Neurosciences; Positron-Emission Tomography; Pyrrolidines - metabolism; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D3 - metabolism; Signal Transduction; Stimulants; Substantia Nigra - metabolism; Tegmentum Mesencephali - metabolism; Tomography; Ventral Tegmental Area - metabolism; Vertebrates: nervous system and sense organs; Young Adult; Human; Neurotransmitter; Dopamine; Catecholamine
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1185778

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.