Striatal Dopamine D2/D3 Receptor Availability Is Reduced in Methamphetamine Dependence and Is Linked to Impulsivity

• Published in: The Journal of neuroscience Vol. 29; no. 47; pp. 14734 - 14740
• Main Authors: Lee, Buyean, London, EdyD, Poldrack, Russell A, Farahi, Judah, Nacca, Angelo, Monterosso, John R, Mumford, Jeanette A, Bokarius, Andrew V, Dahlbom, Magnus, Mukherjee, Jogeshwar, Bilder, Robert M, Brody, Arthur L, Mandelkern, Mark A
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 25.11.2009; Society for Neuroscience
• Subjects: Adult; Amphetamine-Related Disorders - diagnostic imaging; Amphetamine-Related Disorders - metabolism; Amphetamine-Related Disorders - physiopathology; Basal Ganglia - diagnostic imaging; Basal Ganglia - drug effects; Basal Ganglia - metabolism; Biomarkers - analysis; Biomarkers - metabolism; Caudate Nucleus - diagnostic imaging; Caudate Nucleus - drug effects; Caudate Nucleus - metabolism; Corpus Striatum - diagnostic imaging; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dopamine - metabolism; Dopamine Uptake Inhibitors - adverse effects; Down-Regulation - drug effects; Down-Regulation - physiology; Female; Functional Laterality - physiology; Humans; Image Processing, Computer-Assisted; Impulsive Behavior - chemically induced; Impulsive Behavior - metabolism; Impulsive Behavior - physiopathology; Male; Methamphetamine - adverse effects; Neuropsychological Tests; Nucleus Accumbens - diagnostic imaging; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Positron-Emission Tomography; Putamen - diagnostic imaging; Putamen - drug effects; Putamen - metabolism; Receptors, Dopamine D2 - deficiency; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D3 - deficiency; Receptors, Dopamine D3 - drug effects; Young Adult
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/JNEUROSCI.3765-09.2009

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.