Genetic association of GABA-A receptor alpha-2 and Mu opioid receptor with cocaine Cue-reactivity: Evidence for inhibitory synaptic neurotransmission involvement in cocaine dependence

Background: This pilot feasibility study examined the role of genetics in laboratory-induced cocaine craving. Methods: Thirty-four African American, cocaine-dependent male subjects underwent a baseline assessment, cue-exposure session, and genetic analysis. Subjects were classified as either cue-reactive or nonreactive. Results: Among single nucleotide polymorphism markers in 13 candidate genes examined for association with cocaine cue-reactivity, two were statistically significant: GABRA2 (coding for GABA-A receptor alpha-2 subunit; rs11503014, nominal p=.001) and OPRM1 (coding for mu opioid receptor; rs2236256, nominal p=.03). Conclusions: These pilot results suggest that cocaine craving shows variability among cocaine-dependent subjects, and that GABRA2 and OPRM1 polymorphisms have differential influences on cocaine cue-reactivity, warranting studies in future research.