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-subject, double blind, placebo-controlled inpatient human laboratory evaluation of 65 non-treatment seeking, cocaine-dependent (DSM-IV) subjects, aged 18 to 55 years. Participants received both placebo (saline, IV) and cocaine (40mg, IV), and subjective responses were assessed 15 minutes prior to receiving an infusion and at 5-minute intervals for the subsequent 20 minutes. The rs1048101 variant of the α1A-adrenoceptor (ADRA1A) gene was genotyped and 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%) subjects 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 exhibited 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.
Conclusions
This study indicates that 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.