The norepinephrine transporter (SLC6A2; NET) is a third direct target of stimulant drugs (Sulzer et al. 2005). Variants in SLC6A2 have been associated with psychiatric phenotypes including depression (Haenisch et al. 2009; Min et al. 2009), antidepressant response (Min et al. 2009), and panic disorder (Lee et al. 2005). Using our sample of healthy adults (Dlugos et al. 2007) we found that rs36017 (C/C genotype) was associated with increased positive mood, as measured by a composite scale composed of “elation” minus “depression”, following amphetamine administration (20 mg), while rs47958 (C/C genotype) was associated with increased elation. Haplotypes containing these SNPs (rs36017-rs10521329-rs3785155, G–C–C and C–C–A) were also associated with increased positive mood. A follow-up study with a larger number of individuals replicated the association between rs36017 and the POMS Elation scale, as well as with the POMS Vigor scale, and identified a new association between the A/A genotype at rs1861647 and these scales (Dlugos et al. 2009a). In addition, a different haplotype than those mentioned above, which was also constructed from rs36017, rs10521329, and rs3785155 (C–C–G), was associated with increased vigor following amphetamine administration. In sum, these studies suggest that multiple variants in SLC6A2 influence responses to acute amphetamine administration.
