Research On Relieve Effects Of Blocking AMPAR Endocytosis On Pentobarbital Induced Learning And Memory Impairments

Objective: Reports of the effects of pentobarbital on learning and memory are contradictory.Some studies showed no interference with learning and memory by pentobarbital.However,some research showed that pentobarbital caused memory impairment and have long lasting effects.The present study is to explore whether acute local pentobarbital microinjection into hippocampus may affect learning and memory.And if so,whether it can be relieved by the inhibition of AMPAR endocytosis.Methods: Rats weighed 200-250 g were chronically implanted with cannulae above the dorsal hippocampus.Spatial learning and memory were examined by using Morris water maze.Long-term potentiation and long-term drepression of hippocampal CA3-CA1 pathway were tested by electrophysiological recordings in vitro.The action potential of hippocampal CA1 pyramidal neurons was recorded by whole-cell patch-clamp recording.Results: Compared to normal rats,the escape latency and escape distance were much longer in rats that treated with pentobarbital during spatial learning.Similarly,rats treated with pentobarbital spent much less time in the target quadrant during spatial memory retrieval.Additionally,bath application of pentobarbital suppressed LTP in CA3-CA1 pathway and caused LTD-like synaptic depression.Meanwhile,neuronal excitability wasinhibited as reflected by a decrease in the number of AP.However,AMPAR endocytosis inhibitor GluA23 Y peptide significantly relieved the memory impairment induced by pentobarbital and alleviated pentobarbital-induced LTD-like synaptic depression.Conclusion: Acute intrahippocampal administration of pentobarbital can suppress AP and synaptic plasticity which might lead to the impairment of both spatial learning and memory retrieval.More importantly,AMPAR endocytosis inhibitor Glu A23 Y peptide can relieve the impairments.