Impairments produced by amphetamine and stress on memory storage are reduced following a chronic stressful experience

Post-training administration of the psychostimulant, amphetamine or post-trial exposure to restraint stress impaired retention of an inhibitory avoidance response in DBA/2 (DBA) mice. The effect of amphetamine was dose-dependent (1-3 mg/kg) whilst the effect of stress depended on restraint duration (15, 30, or 60 min). Both effects on retention performance appeared to be due to an effect on memory consolidation. In fact, they were observed when the drug and the stressor were experienced at short, but not long, periods of time after training, which is when the memory trace is susceptible to modulation. Moreover, these effects could not be ascribed to a rewarding or non-specific action of the two treatments on retention performance, as the latencies during the retention test of those mice that had not received a footshock during the training, were not affected by the post-training treatments. Administration of either D1 (SCH23390) or D2 [(-)-sulpiride] dopamine (DA) receptor antagonists prior to amphetamine injection or stress exposure antagonized the impairing effects of both treatments. These data indicate that brain dopamine was involved in both cases. Finally, when mice were food restricted for 13 days than allowed free access to food for 24 h before training, either the effects of amphetamine or restraint stress were reduced. Food restricted mice did not differ from control for stepthrough latencies either on the training or the test days, indicating the absence of amnesic or otherwise impairing effects of the experimental procedure per se. Instead, the results indicated hyposensitization to the effects of amphetamine and stress on memory consolidation in food restricted animals.