Subamnesic cycloheximide treatment delays consolidation in mice

In the first experiment, groups of C57 BL/6J mice were given passive avoidance training and then administered different doses of cycloheximide (CYC) immediately, 30 min, or 1 hr after training. Only the highest dose (150 mg/kg) administered immediately or 30 min after training impaired memory when the mice were tested 72 hr after training. In the second experiment, mice were given a nonamnesic administration of CYC (30 mg/kg) or saline immediately after training and another injection of CYC (15 mg/kg, 30 mg/kg, or 75 mg/kg) or saline 1 hr after training. Single injections of CYC and the combination of 30 mg/kg + 15 mg/kg did not impair memory, but the combinations of 30 mg/kg + 30 mg/kg and 30 mg/kg + 75 mg/kg did impair memory. The third experiment demonstrated that brief carbon dioxide anesthetization initiated immediately after training impairs memory. In the fourth experiment, mice were given either saline or 30 mg/kg CYC immediately after training and then subjected to either air or CO2 anesthetization 30 min after training. Only the group given 30 mg/kg CYC + CO2 was amnesic when tested 72 hr after training. The results of these experiments indicate that the administration of a nonamnesic dose of CYC immediately after training renders the memory susceptible to disruption by additional doses of CYC or other amnesic treatments for a longer period of time than normal. It is suggested that CYC delays consolidation and prolongs the labile period of memory formation.