Opioid drugs are of critical medical importance being potent analgesics, but their nonmedical use and abuse has increased worldwide,1 and is associated with high mortality and morbidity.2,3 In addition to being highly addictive, opiate abuse has a strong genetic component with family, twin and adoption studies showing that genetic factors account for at least 40–60% of the overall vulnerability for heroin abuse.4 Genetic associations have been documented between polymorphisms of opioid-related genes and heroin abuse,5–8 but limited information exists about the potential relevance of other neurobiological systems in relation to genetic risk. Neurobiological theories have predominantly posited maladaptions of dopamine and glutamate neurotransmission, and their interaction, as critical for addiction vulnerability, since these neurotransmitters are strongly linked to reward, goal-directed action as well as habitual and compulsive behaviors that characterize addictive disorders.9 Moreover, such behaviors are dependent on the integrity of the striatum, a brain region with prominent interactions between the dopaminergic and glutamatergic systems.
