Effects of phenytoinon the changes of long-term potentiation and amino acid neurotransmitters in rathippocampus induced by chronic stress

Abstract

：Background Chronicstress involves in many mental and physical disorders, while its pathogenesis has not beenfully elucidated. We investigated the changes of long-term potentiation and amino acidneurotransmitters in rat hippocampus induced by chronic stress and the effects ofphenytoin on them. Methods Isolated hippocampal slices of rats were used to observe thechanges of long-term potentiation (LTP) in hippocampal CA1 field usingelectrophysiological technique.Amplitude of population spike (PS) and field excitatorypostsynaptic potentials (fEPSPs) slope were used to indicate the changes of LTP.High-frequency stimulation (HFS) was applied to Schaffer collaterals of hippocampal CA3field, and the changes of PS amplitude and fEPSPs slope in CA1 field were observed. Highperformance liquid chromatography (HPLC) coupled with UV detection was used forquantification of hippocampal amino acids.Results The increases of PS amplitude and fEPSPs slope after HFSin control and stress- phenytoin groups were significantly greater than those instress-saline group (P<0.05).The levels of aspartate in control group weresignificantly lower than those in stress-saline and stress- phenytoingroups(P<0.01);glutamate in control and stress- phenytoin groups were significantlylower than those in stress-saline group(P<0.05);γ-aminobutyric acid(GABA) in stress- phenytoin groups wassignificantly higher than those in control and stress-saline groups(P<0.01).Conclusions Stresscould suppress the development of LTP in hippocampal CA1 field and increase the levels ofhippocampal aspartate and glutamate, but not the level of GABA. Phenytoin could keep LTPnormal in stressed hippocampus, which may be involved in reducing glutamate and increasingGABA. Key words: Stress; Long-term potentiaion; Amino acidneurotransmitters; Hippocampus; Phenytoin