RESUMEN
Objective To investigate the effects of proteasome inhibitor MG132 on memory acquisition and memory retrieval in one-trail passive avoidance for mice.Methods MG132 (25 mg/kg) was administrated at different time points to analyze the time-dependent effects of MG132 on hippocampus proteasome activity.MG132 (25 mg/kg) was administrated 3 hours before-training or 1.5 hours pre-test to investigate the effect on memory acquisition and retrieval.The interaction of low dose (12 mg/kg) of MG132 and novelty interference on memory retrieval to studied.Results Hippocampus proteasome activity was significantly blocked when MG132 (25 mg/kg) was administrated 0.5-1.5 hours before analysis.The inhibition recovered as time passing and backed to normal state 24 hours later.A significant difference was showed between vehicle and pre-training,pre-test group (pre-training vehicle (296.03 ± 3.97) s,pre-training (173.30 ± 47.51) s ; pre-test vehicle (199.23 ± 43.01) s,pre-test (44.10 ± 11.16) s).Proteasome inhibitor did not produce a significant effect on memory retrieval (vehicle (174.19 ± 30.54)s,lower dose (174.19± 30.54)s),then only together with a novelty task the retrieval was significantly altered(vehicle (164.02 ±35.26)s,MG132 +novelty group (84.70 ±23.92)s).Conclusion Proteasome inhibitor MG132 can inhibit memory acquisition and memory retrieval.Thereby the effect on memory retrieval is enhanced by novelty.Thus,a physiological proteasome activity is essential for learning abilities.