Further evidence of association between amphetamine  response and SLC6A2 gene variants.
OBJECTIVE
We previously found that the intronic norepinephrine transporter gene (SLC6A2) polymorphism rs36017 modulates feelings of elation after administration of 20 mg D-amphetamine in healthy volunteers.


OBJECTIVE
In this study, we further investigated the association between D-amphetamine response and 11 SLC6A2 single-nucleotide polymorphisms (SNPs), including rs36017, in an extended sample of Caucasian young adults.


METHODS
One hundred fifty-nine healthy volunteers participated in a three-session double-blind crossover design receiving either placebo or oral D-amphetamine (10 and 20 mg). Based on our previous results, we examined the associations between levels of self-reported elation and vigor after D-amphetamine administration and SNPs and SNP haplotypes in SLC6A2.


RESULTS
Consistent with our previous findings, SNPs rs36017 and rs1861647 were associated with significantly higher ratings of elation and vigor after 20 mg Damphetamine. Ratings of vigor after 20 mg D-amphetamine were also associated with a two-SNP haplotype formed with rs1861647 and rs5569 and a three-SNP haplotype formed with rs36017, rs10521329, and rs3785155.


CONCLUSIONS
These results provide further evidence that genetic variants in the SLC6A2 gene are involved in acute response to D-amphetamine, which may influence progression to amphetamine abuse. Identifying sources of variation in acute drug responses could lead to better prevention and treatment of psychostimulant abuse and may be valuable in the therapeutic use of stimulants.
Dlugos
Andrea M
AM
Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, 5841 South Maryland Avenue, MC3077 Chicago, IL, USA.
Hamidovic
Ajna
A
Palmer
Abraham A
AA
de Wit
Harriet
H
D000293:Adolescent; D000328:Adult; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D018592:Cross-Over Studies; D003913:Dextroamphetamine / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People; D055815:Young Adult
D000697:Central Nervous System Stimulants; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D003913:Dextroamphetamine