The α-1 adrenoceptor (ADRA1A) genotype moderates the magnitude of acute cocaine-induced subjective effects in cocaine-dependent individuals

Daryl Shorter, David A. Nielsen, Sara C. Hamon, Ellen M. Nielsen, Thomas R. Kosten, Thomas F. Newton, Richard De La Garza

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Objectives We examined whether a functional variant of the ADRA1A gene moderated cocaine-induced subjective effects in a group of cocaine-dependent individuals. Methods This study was a within-participant, double-blind, placebo-controlled inpatient human laboratory evaluation of 65 nontreatment-seeking, cocaine-dependent [Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSMIV)] individuals aged 18-55 years. Participants received both placebo (saline, IV) and cocaine (40 mg, IV), and subjective responses were assessed 15 min before receiving an infusion and at 5 min intervals for the subsequent 20 min. The rs1048101 variant of the α1Aadrenoceptor (ADRA1A) gene was genotyped and it was evaluated whether the Cys to Arg substitution at codon 347 in exon 2 (Cys347Arg) moderated the magnitude of the subjective effects produced by cocaine. Results Thirty (46%) participants were found to have the major allele CC genotype and 35 (44%) carried at least one minor T-Allele of rs1048101 (TT or TC genotype). Individuals with the CC genotype showed greater responses for 'desire' (P<0.0001),'high' (P<0.0001),'any drug effect' (P<0.0001), 'like cocaine' (P<0.0001), and 'likely to use cocaine if given access' (P<0.05) with experiment-wise significance. Conclusion This study indicates that the ADRA1A genotype could be used to identify individuals for whom acute cocaine exposure may be more rewarding and by inference may result in greater difficulty in establishing and/ or maintaining abstinence from cocaine.

Original languageEnglish (US)
Pages (from-to)428-435
Number of pages8
JournalPharmacogenetics and Genomics
Volume26
Issue number9
DOIs
StatePublished - Sep 1 2016

Keywords

  • ADRA1A
  • cocaine
  • genotype
  • polymorphism
  • subjective effects

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'The α-1 adrenoceptor (ADRA1A) genotype moderates the magnitude of acute cocaine-induced subjective effects in cocaine-dependent individuals'. Together they form a unique fingerprint.

Cite this