The role of central DA systems in the acute effects of drugs of abuse was recognized long ago (Wise, 1980, 1987; Di Chiara and Imperato, 1988). Even before (Ahlenius et al., 1973), attempts were made to prevent human alcohol-induced euphoria through administration of the DA synthesis inhibitor alpha methyl-para-tyrosine. Although theoretically ineccepibile, this approach (reduction of drug-induced DA increments to prevent abuse) is unlikely to have a practical validity as any compound with DA antagonistic (i.e., neuroleptics) properties is known to be aversive in humans. On the other hand, widely documented experimental evidence suggests that the mesolimbic dopamine system is “hypofunctional” in the addicted brain (Melis et al., 2005). In brief, the hypothesis contends that decreased DA function in addicted subjects results in a decreased interest to non-drug-related stimuli and increased sensitivity to the drug of choice (Melis et al., 2005), leading to propose that restoring DA function might be therapeutically advantageous.
