Effect of nucleus accumbens dopamine depletion on motivational aspects involved in initiation of cocaine and heroin self-administration in rats.

The involvement of mesolimbic dopamine (DA) systems in motivational aspects of drug-taking behavior during initiation of drug self-administration was investigated using a recently developed behavioral paradigm. In separate experiments animals were allowed to self-administer cocaine or heroin (0.16 and 0.32 mg . kg-1 per inf) during 5 consecutive daily 3-h sessions. During a 15-min period preceding the last four self-administration sessions lever-press behavior was measured in absence of the drug as an index of the motivational aspects involved in drug-taking behavior. The effect of 6-hydroxydopamine (6-OHDA) lesion of the nucleus accumbens (NAC) on lever-press behavior before and during self-administration was measured. Destruction of DA terminals in the NAC did not affect initiation of heroin self-administration nor the lever-press behavior during the period preceding the self-administration sessions. In cocaine animals 6-OHDA lesion of the NAC decreased the total intake of cocaine during the self-administration sessions and impaired discriminative lever-responding for the drug, both during cocaine self-administration, and during preceding periods when no cocaine was available. It is concluded that DAergic systems in the NAC might be involved in the reinforcement and/or motivational processes underlying cocaine self-administration. The present findings, however, do not support the notion of a critical role of NAC DA in the motivational aspects of drug-taking behavior in general.