title: Polymorphisms in dopamine transporter (SLC6A3) are associated with stimulant effects of D-amphetamine: an exploratory pharmacogenetic study using healthy volunteers.
abstract: Individuals vary in their subjective responses to stimulant drugs, and these differences are believed to be partially genetic in origin. We evaluated associations between mood, cognitive and cardiovascular responses to d-amphetamine and four polymorphisms in the dopamine transporter (SLC6A3): rs460000, rs3756450, rs37022 and rs6869645. Healthy Caucasian male and female volunteers (N = 152) participated in a double-blind, crossover design study in which they received placebo, 10 and 20 mg of d-amphetamine. We measured self-reported rating of mood, performance on the Digit Symbol Substitution Task, blood pressure and heart rate. Individuals with the C/C genotype at rs460000 (N = 83) reported approximately twofold higher ratings of stimulation and euphoria relative to the A/A+A/C (N = 69) genotype group, at both the 10 and 20 mg doses. No other responses or SNPs showed significant effects. rs460000 is in perfect LD with rs463379 (CEU: D' = 1; r (2) = 1), which was not studied here, but has been associated with etiology of Attention Deficit Hyperactivity Disorder (ADHD). These findings suggest a pleiotropic effect of this polymorphic locus on both ADHD and sensitivity to the subjective effects of amphetamine.
authors.affiliation: The University of Chicago, Chicago, IL, USA.
authors.forename: Ajna
authors.initials: A
authors.lastname: Hamidovic
authors.forename: Andrea
authors.initials: A
authors.lastname: Dlugos
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Palmer
authors.forename: Harriet
authors.initials: H
authors.lastname: de Wit
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D018592:Cross-Over Studies; D003913:Dextroamphetamine / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D010919:Placebos; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D010919:Placebos; C493214:SLC6A3 protein, human; D003913:Dextroamphetamine