STRAIN-DEPENDENT EFFECTS OF POST-TRAINING COCAINE OR NOMIFENSINE ON MEMORY STORAGE INVOLVE BOTH D-1 AND D-2 DOPAMINE-RECEPTORS

Post-training administration of cocaine (1-10 mg/kg) or nomifensine (1 -10 mg/kg) dose-dependently improves retention of an inhibitory avoida nce response in C57BL16 mice, while impairing it in the DBA/2 strain. The effects on retention performance induced by the psychostimulant an d the dopamine (DA) reuptake blocker in C57BL/6 and DBA/2 mice appear to be due to an effect on memory consolidation In fact, they were obse rved when drugs were given at short, but not long, periods of time aft er training, i.e. when the memory trace is susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rew arding or nonspecific action of the drugs on retention performance, as the latencies during the retention test of those mice that had not re ceived a footshock during the training were not affected by the post-t raining drug administration. The strain-dependent effects of an interm ediate dose (5 mg/kg) of both cocaine and nomifensine were reversed by pretreatment with either selective D-1 or D-2 DA receptor antagonists SCH 23390 and (-)-sulpiride administered at per se non-effective dose s (0.025 and 6 mg/kg, respectively), thus suggesting that D-1 and D-2 receptor types are similarly involved in modulating memory processes. These results show that the effects of cocaine on memory consolidation are related to its dopaminergic action, since they are similar to tho se produced by nomifensine and, what is more important, are antagonize d by pretreatment with DA receptor antagonists. Moreover, they point t o possible genotype-dependent factors in DA mediated effects of cocain e on memory consolidation, indicating inbred mice as an experimental t ool to investigate neural mechanisms underlying interindividual suscep tibility to drug addiction.