氯胺酮对大鼠海马脑片突触长时程增强效应的影响

目的：观察氯胺酮对大鼠海马脑片突触长时程增强(LTP)效应的影响，并探讨其影响记忆的机制。方法：98只雄性SD大鼠，断头后取出海马组织，制备厚400 μm的海马脑片。取49张脑片，随机分为7组：对照组、氯胺酮1、5、10、30、50和100 μmol•L^-1组。各组脑片分别灌流人工脑脊液(ACSF)、氯胺酮1、5、10、30、50和100 μmol•L^-1。采用细胞外微电极记录技术，记录海马脑片CA1区细胞外群体峰电位(PS)的变化。另取49张脑片，随机分为7组：LTP组、氯胺酮LTP 1、5、10、30、50和100 μmol•L^-1组。各组脑片分别灌流ACSF、氯胺酮1、5、10、30、50和100　μmol•L^-1。海马脑片记录PS 30 min后，施以100 Hz的高频强直刺激(HFS)，诱发LTP，观察各组脑片HFS后PS幅值的变化。结果：与对照组比较，氯胺酮1、5和10 μmol•L^-1组给药后PS幅值无明显改变(P>0.05)，氯胺酮30、50和100 μmol•L^-1组给药后PS幅值明显降低(P<0.01)。LTP组HFS后PS幅值增高，较刺激前增加了(52±12)% (P<0.01)。与LTP组比较，氯胺酮LTP 1和5 μmol•L^-1组HFS后其PS幅值无明显改变(P>0.05)，氯胺酮LTP 10、30、50和100 μmol•L^-1组HFS后其PS幅值均明显降低(P<0.01)。结论：氯胺酮能够抑制海马LTP的形成而影响记忆功能，其机制与抑制海马N-甲基-D-门冬氨酸(NMDA)受体有关。

Effect of ketamine on synaptic long-term potentiation in hippocampal slices of rats

Objective To investigate the effect of ketamine on the synaptic long-term potentiation(LTP) in the CA1 area of rat hippocampal slices,and to elucidate the mechanisms underlying the effect of ketamine on memory.Methods Hippocampal slices(400 μm thick) were obtained from the brains of male Sprague-Dawley rats(2 months old) weighing 200-250 g that were decapitated.The slices were incubated in artificial cerebrospinal fluid(ACSF) at room temperature for at least 120 min before use.Forty-nine slices were randomly divided into 7 groups(n=7):control group,ketamine 1,5,10,30,50 and 100 μmol·L-1 groups.All the slices in each group were perfused with ACSF,ketamine 1,5,10,30,50 or 100 μmol·L-1,respectively.The slices in each group were performed to record evoked population spikes(PS) using extracellular microelectrode recording technique.Another forty-nine slices were randomly divided into 7 groups(n=7):LTP group,ketamine-LTP 1,5,10,30,50 and 100 μmol·L-1 groups.All the slices in each group were perfused with ACSF,ketamine 1,5,10,30,50 or 100 μmol·L-1,respectively.PSs were recorded for at least 30 min before LTP in each group.For LTP induction,high-frequency stimulation(HFS) conditioning pulses(100 Hz·s-1) were applied to the Schaffer collateral-commissural pathway of hippocampus using a bipolar stimulating electrode.The changes in PS amplitude after HFS were analyzed in each group.Results The PS amplitude of the rat hippocampal slices in ketamine 1,5,and 10 μmol·L-1 groups had no significant difference compared with control group.The PS amplitude in ketamine 30,50 and 100 μmol·L-1 groups decreased compared with control group(P<0.01).The PS amplitude in group LTP after HFS was significantly increased by(52±12)% compared with pre-HFS,it indicated the successful induction of LTP.The amplitudes of the PS in ketamine-LTP 1 and 5 μmol·L-1 groups did not significantly change after HFS,when compared with LTP group.Compared with LTP group,the amplitudes of the PS in ketamine-LTP 10,30,50 and 100 μmol·L-1 groups after HFS decreased significantly(P<0.01).Conclusion The inhibition of LTP induction in hippocampus of rats may contribute to ketamine-induced deficits in memory,and the underlying mechanism is involved in the inhibition of N-methyl-D-aspartate(NMDA) receptor in hippocampus.