title: Genetic variation of the dopamine transporter (DAT1) influences the acute subjective responses to cocaine in volunteers with cocaine use disorders.
abstract: OBJECTIVE
  The aim of this study was to identify gene variants of DAT1 (SLC6A3) that modulate subjective responses to acute cocaine exposure.
  
  
  METHODS
  Non-treatment-seeking volunteers (n=66) with cocaine use disorders received a single bolus infusion of saline and cocaine (40 mg, intravenous) in a randomized order. Subjective effects were assessed with visual analog scales administered before (-15 min) and up to 20 min after infusion. Ratings of subjective effects were normalized to baseline, and saline infusion values were subtracted. Data were analyzed using repeated measures analysis of variance. DNA from the participants was genotyped for the DAT1 intron 8 (rs3836790) and 3'-untranslated region (rs28363170) variable number of tandem repeats.
  
  
  RESULTS
  Participants were mostly male (∼80%) and African American (∼70%). No differences were found among drug use variables between groups for either polymorphism. Carriers of the 9-allele of the DAT1 3'-untranslated region (9,9 and 9,10) exhibited greater responses to cocaine for 'high', 'any drug effect', 'anxious', and 'stimulated' (all P-values<0.001) compared with individuals homozygous for the 10-allele. For the intron 8 polymorphism, individuals homozygous for the 6-allele exhibited greater responses for 'anxious' compared with carriers of the 5-allele (P<0.001). Individuals possessing the genotype pattern of 10,10 and at least one 5-allele reported lower responses to 'good effects', 'bad effects', 'depressed', and 'anxious' (all P-values<0.01).
  
  
  CONCLUSIONS
  The data presented here show for the first time support for the hypothesis that genetic differences in DAT1 contribute to the variation in subjective responses to cocaine among participants with cocaine use disorders.
authors: aDepartment of Pharmacology bMenninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine cMichael E. DeBakey Veterans Affairs Medical Center, Houston, Texas dLaboratory of Statistical Genetics, The Rockefeller University, New York, New York, USA.
authors: Alex J
authors: AJ
authors: Brewer
authors: David A
authors: DA
authors: Nielsen
authors: Catherine J
authors: CJ
authors: Spellicy
authors: Sara C
authors: SC
authors: Hamon
authors: Justin
authors: J
authors: Gingrich
authors: Daisy G Y
authors: DG
authors: Thompson-Lake
authors: Ellen M
authors: EM
authors: Nielsen
authors: James J
authors: JJ
authors: Mahoney
authors: Thomas R
authors: TR
authors: Kosten
authors: Thomas F
authors: TF
authors: Newton
authors: Richard
authors: R
authors: De La Garza
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000483:Alleles; D001794:Blood Pressure / Q000235:genetics; D003042:Cocaine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019970:Cocaine-Related Disorders / Q000235:genetics* / Q000473:pathology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006339:Heart Rate / Q000235:genetics; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019966:Substance-Related Disorders / Q000235:genetics* / Q000473:pathology; D011795:Surveys and Questionnaires
chemical_list: D020413:3' Untranslated Regions; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D003042:Cocaine