Intense training abolishes the two temporal windows of cycloheximide-induced amnesia in rats

Several studies have identified two distinct time windows during memory consolidation that are sensitive to protein synthesis inhibitors, whereas only a single window is observed following enhanced training. These findings suggest that one or two waves of protein synthesis may be required for long-term memory formation, depending on the strength of the training. However, further intensifying the learning stimulus may counteract the disruptive effects of protein synthesis inhibitors. To test this hypothesis, we trained rats in an inhibitory avoidance task using either moderate or intense footshock. Rats then received systemic injections of a protein synthesis inhibitor at -0.5 h before training, or at 1.0, 2.5, or 5.5 h after training. Following moderate training, amnesia was observed when the inhibitor was administered at -0.5 or 2.5 h, but not at 1.0 or 5.5 h. In contrast, after intense training, the inhibitor had no effect on memory consolidation at any of these intervals. Together, these results indicate that memory consolidation induced by intense training is resistant to disruption by protein synthesis inhibition.