THE EFFECTS OF MORPHINE ON MEMORY CONSOLIDATION IN MICE INVOLVE BOTH D1 AND D2 DOPAMINE-RECEPTORS

Post-training administration of morphine (0.25, 0.5, or 1 mg/kg) dose-dependently impairs retention of an inhibitory avoidance response in mice. The effects on retention performance induced by the drug appear to be due to an effect on memory consolidation. In fact, they were observed when drugs were given at short, but not long, periods of time after training, i.e., when the memory trace was susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rewarding or nonspecific action of the drugs on retention performance, because the latencies during the retention test of those mice that had not received a footshock during the training were not affected by post-training drug administration. Pretreatment with either selective D1 or D2 dopamine (DA) receptor antagonists SCH 23390 and (-)-sulpiride administered at per se noneffective doses (0.025 and 6 mg/kg, respectively) potentiated the effects of morphine, while either selective D1 or D2 receptor agonists SKF 38393 and LY 171555 at per se noneffective doses (5 and 0.25 mg/kg, respectively) antagonized the effects of the opiate on memory consolidation. No significant differences were evident between the effects of D1 and D2 receptor active compounds, thus suggesting that D1 and D2 receptor types are similarly involved in the effects of morphine on memory consolidation, in agreement with previously reported results. These results are discussed in terms of a possible inverse relationship of endogenous opioid and DA systems in the brain that are involved in memory processes. (C) 1994 Academic Press, Inc.