title: Striatal dopamine d2/d3 receptor availability is reduced in methamphetamine dependence and is linked to impulsivity.
abstract: While methamphetamine addiction has been associated with both impulsivity and striatal dopamine D(2)/D(3) receptor deficits, human studies have not directly linked the latter two entities. We therefore compared methamphetamine-dependent and healthy control subjects using the Barratt Impulsiveness Scale (version 11, BIS-11) and positron emission tomography with [(18)F]fallypride to measure striatal dopamine D(2)/D(3) receptor availability. The methamphetamine-dependent subjects reported recent use of the drug 3.3 g per week, and a history of using methamphetamine, on average, for 12.5 years. They had higher scores than healthy control subjects on all BIS-11 impulsiveness subscales (p < 0.001). Volume-of-interest analysis found lower striatal D(2)/D(3) receptor availability in methamphetamine-dependent than in healthy control subjects (p < 0.01) and a negative relationship between impulsiveness and striatal D(2)/D(3) receptor availability in the caudate nucleus and nucleus accumbens that reached statistical significance in methamphetamine-dependent subjects. Combining data from both groups, voxelwise analysis indicated that impulsiveness was related to D(2)/D(3) receptor availability in left caudate nucleus and right lateral putamen/claustrum (p < 0.05, determined by threshold-free cluster enhancement). In separate group analyses, correlations involving the head and body of the caudate and the putamen of methamphetamine-dependent subjects and the lateral putamen/claustrum of control subjects were observed at a weaker threshold (p < 0.12 corrected). The findings suggest that low striatal D(2)/D(3) receptor availability may mediate impulsive temperament and thereby influence addiction.
authors: Department of Psychiatry, Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90024, USA.
authors: Buyean
authors: B
authors: Lee
authors: Edythe D
authors: ED
authors: London
authors: Russell A
authors: RA
authors: Poldrack
authors: Judah
authors: J
authors: Farahi
authors: Angelo
authors: A
authors: Nacca
authors: John R
authors: JR
authors: Monterosso
authors: Jeanette A
authors: JA
authors: Mumford
authors: Andrew V
authors: AV
authors: Bokarius
authors: Magnus
authors: M
authors: Dahlbom
authors: Jogeshwar
authors: J
authors: Mukherjee
authors: Robert M
authors: RM
authors: Bilder
authors: Arthur L
authors: AL
authors: Brody
authors: Mark A
authors: MA
authors: Mandelkern
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007175:Impulsive Behavior / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D009483:Neuropsychological Tests; D009714:Nucleus Accumbens / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000172:deficiency* / Q000187:drug effects; D050637:Receptors, Dopamine D3 / Q000172:deficiency / Q000187:drug effects; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D008694:Methamphetamine; D004298:Dopamine