Striatal dopamine d2/d3 receptor availability is reduced in methamphetamine dependence and is linked to impulsivity.

TitleStriatal dopamine d2/d3 receptor availability is reduced in methamphetamine dependence and is linked to impulsivity.
Publication TypeJournal Article
Year of Publication2009
AuthorsLee, B, London ED, Poldrack RA, Farahi J, Nacca A, Monterosso JR, Mumford JA, Bokarius AV, Dahlbom M, Mukherjee J, Bilder RM, Brody AL, Mandelkern MA
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume29
Issue47
Pagination14734-40
Date Published2009 Nov 25
ISSN1529-2401
KeywordsAdult, Amphetamine-Related Disorders, Basal Ganglia, Biological Markers, Caudate Nucleus, Corpus Striatum, Dopamine, Dopamine Uptake Inhibitors, Down-Regulation, Female, Functional Laterality, Humans, Image Processing, Computer-Assisted, Impulsive Behavior, Male, Methamphetamine, Neuropsychological Tests, Nucleus Accumbens, Positron-Emission Tomography, Putamen, Receptors, Dopamine D2, Receptors, Dopamine D3, Young Adult
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.

Alternate JournalJ. Neurosci.