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Further evidence of association between amphetamine response and SLC6A2 gene variants

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Abstract

Background and rationale

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.

Objectives

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 d-amphetamine. 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.

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Acknowledgements

We gratefully thank Dr. Andrew Skol, Dr. David Goldman, Dr. Colin Hodgkinson, and Pei-Hong Shen for their invaluable input and technical support. We also thank Ms. Margo Meverden and Ms. Patricia Kriegel for their skillful technical assistance. This work was supported by DA021336, DA02812, and MO RR00055.

Ethical standards

The experiments comply with the current laws of the United States where they were performed.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, 5841 South Maryland Avenue, MC3077, Chicago, IL, USA

    Andrea M. Dlugos, Ajna Hamidovic, Abraham A. Palmer & Harriet de Wit

  2. Department of Human Genetics, The University of Chicago, Chicago, IL, USA

    Abraham A. Palmer

Authors
  1. Andrea M. Dlugos
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  2. Ajna Hamidovic
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  3. Abraham A. Palmer
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  4. Harriet de Wit
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Correspondence to Harriet de Wit.

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Dlugos, A.M., Hamidovic, A., Palmer, A.A. et al. Further evidence of association between amphetamine response and SLC6A2 gene variants. Psychopharmacology 206, 501–511 (2009). https://doi.org/10.1007/s00213-009-1628-y

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  • DOI: https://doi.org/10.1007/s00213-009-1628-y

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