Abstract

The conditioned place preference paradigm was used to study the reinforcing properties ofD-amphetamine. Rats were injected (i.p.) withD-amphetamine sulphate (0.5, 1.0 or 5.0 mg/kg) and 10 min later confined for 30 min to one side of a shuttle ☐ in which each of the two compartments had distinctive features. On alternate (control) days they received saline injections and were confined for 30 min to the opposite side. At all dosesD-amphetamine produced place preference for the distinctive compartment that previously had been associated with the drug. Pretreatment with haloperidol (0.15 or 1.0 mg/kg) antagonized the place preference produced by amphetamine (1.5 mg/kg). By itself, haloperidol (0.15 or 1.0 mg/kg) did not produce place aversion. In separate experiments theD-amphetamine-induced place preference was examined in rats that had received 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens. Animals with the greatest depletion of dopamine did not show preference for the compartment associated withD-amphetamine. Furthermore, the time spent on the amphetamine-reinforced side correlated significantly with the levels of dopamine remaining in the nucleus accumbens but not with the dopamine content in the striatum. Depletion of peripheral catecholamines by systemic injections of 6-OHDA did not affectD-amphetamine-induced place preference conditioning. Other groups of animals that received the dopamine receptor agonist, apomorphine, also developed a conditioned preference for the compartment that had been associated with the drug treatment. These findings support the view that the reinforcing effects ofD-amphetamine are mediated by central dopamine-containing neurons, and in particular those of the mesolimbic system.