DNQX IN THE NUCLEUS-ACCUMBENS INHIBITS COCAINE-INDUCED CONDITIONED PLACE PREFERENCE

Several lines of evidence suggest that activation of both AMPA/kainate receptors and dopaminergic receptors in the nucleus accumbens may be required for psychostimulant drug induced reward. However, it has been reported that dopaminergic antagonists fail to block acquisition of c onditioned place preference to cocaine. The goal of these experiments was to determine whether AMPA receptor antagonists injected into the n ucleus accumbens could block conditioned place preference elicited by cocaine under conditions where dopaminergic antagonists do not inhibit acquisition of place preference. DNQX (1 mu g/0.5 mu l), injected int o the nucleus accumbens just before systemic injections of cocaine (20 mg/kg i.p.) during the training sessions, attenuated the acquisition of place preference. This suggests that AMPA receptors are involved in acquisition of place preference to cocaine. By contrast, fluphenazine (2.5 mu g/0.5 mu l), injected into the nucleus accumbens during train ing, did not alter cocaine-induced place preference. Analysis of locom otor activity showed that the ability of flyphenazine to inhibit cocai ne-induced hyperactivity progressively decreased with each training se ssion. These observations suggest that the failure of dopaminergic ant agonists to block cocaine-induced place preference may be related to a daptations occurring following repeated exposure to these drugs. Both DNQX and fluphenazine blocked the expression of conditioned place pref erence in rats that had been previously trained with cocaine alone. Th is result suggests that both AMPA and dopaminergic receptors are invol ved in the expression of a conditioned place preference to cocaine.