POTENTIATION OF THE EFFECTS OF REWARD-RELATED STIMULI BY DOPAMINERGIC-DEPENDENT MECHANISMS IN THE NUCLEUS-ACCUMBENS

Three experiments examined the behavioural, pharmacological and neural specificity of the previously reported potentiation of responding with conditioned reinforcement following intra-accumbens d-amphetamine, by studying the effects of intra-accumbens dopamine (DA) and noradrenaline, using an acquisition of a new response procedure. In experiment 1, the effects of intra-cerebral DA infusions (5, 20, 50-mu-g/2-mu-l) were compared in four conditions: (i) intra-accumbens DA following positive pairing of the conditioned stimulus (CS) and water during training; (ii) as (i) but also following a systemic dose of the DA receptor antagonist alpha-flupenthixol; (iii) intra-accumbens DA following random pairing of the CS and water during training; and (iv) as (i) but with intra-caudate rather than intra-accumbens DA. The results showed that only with intra-accumbens DA in the positive pairing condition was there a significant dose-dependent increase in responding. In experiment 2, the effects of a higher range of doses (20, 100, 200-mu-g) and smaller infusion volume (5, 25, 50-mu-g/1-mu-l) of intra-accumbens DA were studied, in comparison with a similar range of doses (5, 25, 50-mu-g/1-mu-l) of intra-accumbens noradrenaline (NA). Only DA produced a selective, dose-dependent increase in responding with conditioned reinforcement. In experiment 3 neurotoxic lesions of the dorsal noradrenergic bundle (DNAB) using 6-hydroxydopamine producing profound (about 90%) depletion of cortical and nucleus accumbens NA levels had no effect on the increased responding with conditioned reinforcement produced by intra-accumbens d-amphetamine (3, 10, 30-mu-g/1-mu-l). The results are discussed in terms of the neurochemical mediation of the potentiation of the effects of conditioned reinforcers by d-amphetamine and the role of DA-dependent mechanisms of the nucleus accumbens in reward-related processes.