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. © 2010 Springer Science+Business Media, LLC.
Hamidovic, A., Dlugos, A., Palmer, A. A., & De Wit, H. (2010). Polymorphisms in dopamine transporter (SLC6A3) are associated with stimulant effects of d-amphetamine: An exploratory pharmacogenetic study using healthy volunteers. Behavior Genetics, 40(2), 255–261. https://doi.org/10.1007/s10519-009-9331-7