Dopamine transporter gene associated with diminished subjective response to amphetamine.

  • Lott D
  • Kim S
  • Cook E
 et al. 
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Individual variability in responses to stimulant drugs may influence risk of stimulant abuse and treatment response. However, the genetic determinants of this variability have yet to be elucidated. The dopamine transporter is an important site of amphetamine action. Therefore, the dopamine transporter gene (DAT1) is a logical candidate gene to study. Using a drug challenge approach, we tested for association between DAT1 genotype and subjective responses to amphetamine in healthy adults. Volunteers participated in a double-blind, crossover design, randomly receiving placebo, 10 mg, and 20 mg oral D-amphetamine, and completed self-report measures on subjective effects including anxiety and euphoria. Subjects were genotyped for the DAT1 3'-untranslated region VNTR polymorphism and divided into groups based on genotype: homozygous for nine repeats (9/9, N=8), heterozygous (9/10, N=36) and homozygous for 10 repeats (10/10, N=52). The effects of amphetamine on ratings of Feel Drug, Anxiety, and Euphoria were examined with ANCOVA. In 9/10 and 10/10 subjects, amphetamine produced its expected effects of increased Euphoria, Anxiety, and Feel Drug (p

Author-supplied keywords

  • 3' Untranslated Regions
  • Adolescent
  • Adult
  • Amphetamine
  • DNA Primers
  • Dopamine Plasma Membrane Transport Proteins
  • Female
  • Gene Expression Regulation
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Minisatellite Repeats
  • Nerve Tissue Proteins
  • Reference Values
  • drug effects
  • genetics
  • pharmacology

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  • David C Lott

  • Soo-Jeong Kim

  • Edwin H Jr Cook

  • Harriet de Wit

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