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


Dr. Smelson, Department of Psychiatry, University of Massachusetts Medical School, 55 Lake Ave., Worcester, MA 01655. E-mail:


Background: This pilot feasibility study examined the role of genetics in laboratory-induced cocaine craving.

Methods: Thirty-four African American, cocaine-depend-
ent 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. (Am J Addict 2012;21:411–415)