Opiates and cocaine have different mechanisms of action in the CNS and may interact differently with GABRA2 variation and early life stress to influence the vulnerability to heroin or cocaine dependence. Our finding of a GABRA2-heroin dependence association is backed up by preclinical studies that indicate that GABAA receptors may influence the actions of opiates; for example, hyperpolarization of GABAergic neurons in the ventral tegmental area (where GABAA α2 receptors are highly expressed) by opiates results in increased firing of dopamine neurons within the dopamine reward pathway (8–10,48–52).
