Effects of systemic and intra-hippocampal injections of cycloheximide on the late reconsolidation of fear-based memory in rats

Reactivation of a stabilized memory induces a second wave of consolidation process which is now called as reconsolidation. Recently, a late consolidation process was proposed, suggesting that memory after learning within a delayed time window was labile. This late memory consolidation needs protein synthesis in the hippocampus. The aim of this study was to test whether the re-stabilized memory after reactivation also requires a late-phase protein synthesis in the hippocampus. We also investigated whether memories become increasingly resistant to disruption with age. Male Wistar rats were trained in a one trial passive avoidance task (1mA, 3s). In the first experiment, cycloheximide (CYC, 2.8 mg/kg, i.p.) administrated 15 minutes before the memory reactivation and also 3, 6, 12 and 24 hours after the memory reactivation. In the second experiment, the same dose of CYC administrated to rats with memory age of 7, 14, 28 or 56 days. In the third experiment, CYC administrated (4 µg or 8µg/µl) into hippocampus. In the last experiment, CYC administrated (8µg/µl) into hippocampus of rats with memory age of 7, 14, 28 or 56 days. In all experiments, memory test was done 2 and 7 days after memory reactivation. Results indicated that systemic administration of CYC only 12h after memory reactivation significantly impaired memory retention. With increasing the age of memory, no effect of CYC was found. This impairing effect also was found when CYC was injected into hippocampus. This impairing effect also was found on memory age with 7 days. Our findings indicate that protein synthesis, particularly in the hippocampus, plays an important role in the late memory reconsolidation and with increasing the age of memories, they become resistant to disruption.