脑内5-羟色胺减少对致痫大鼠癫痫发作及学习记忆的影响

目的:于中脑正中中缝核局部微量注射5,7-二羟色胺(5,7-DHT),探讨5-羟色胺(5-HT)与癫痫的关系及匹罗卡品(PILO)致痫大鼠学习记忆改变的可能机制。方法:成年SD大鼠随机分为PILO组、PILO+5,7-DHT组、空白对照组三组,然后根据是否出现癫痫持续状态(SE)再将PILO组分成:PILO+SE组和PILO-SE组两亚组;利用视频脑电图观察大鼠癫痫发作及皮层脑电变化;运用Morris水迷宫测评大鼠空间学习记忆水平;最后运用免疫组化法观察大鼠中缝核5-HT能神经元。结果:大鼠予以5,7-DHT(PILO+5,7-DHT组)处理后造模成功率、死亡率及慢性期自发性发作频率均增高;与空白组比较PILO+SE组中缝核5-HT能神经元数目有所下降(P<0.05),而PILO+5,7-DHT组下降更明显(P<0.01);与空白组比较PILO+SE组平均逃避潜伏期延长、穿越平台次数减少、原平台象限停留时间缩短(P<0.05),而与PILO+SE组比较PILO+5,7-DHT组变化不明显。结论:脑内5-HT水平的降低容易诱发癫痫发作,尚不能认为癫痫大鼠合并认知功能障碍与脑内5-HT水平下降有关。

Effect of serotonin depletion on seizures learning-memory in pilocarpine-induced epileptic rats

Objective: To investigate the relationship between serotonin(5-HT)and epilepsy and the mechanism of learning-memory in pilocarpine(PILO)-induced epileptic rats after 5,7-dihydroxytryptamine(5,7-DHT) microinjection in median raphe nucleus.Methods: Adult S D rats were randomly divided into 3 groups: PILO group,PILO+ 5,7-DHT group,vehicle control group;PILO group was divided into two groups by status epilepticus(SE): PILO+SE group and PILO-SE group.The rats’ seizures and cortex electroencephalography(EEG) were observed by vedio EEG. The rats’ spatial learning-memory was evaluated by Morris water maze.Finally,serotonergic neuron in raphe nuclei was observed by immunohistochemisty.Results: After treatment of 5,7-DHT(PILO+5,7-DHT group),the success rate,the mortality and the frequency of chronic spontaneous seizures in pilocarpine-induced epilepsy model were all improved.Compared with the control group,the number of serotonergic neuron in raphe nuclei was decrease in PILO+SE group(P<0.05).Moreover,it’s extremely decrease in PILO+5,7-DHT group(P<0.01).Compared with control group,the mean escape latency was prolonged,the times of crossing target was decreased and the retention time in target zone was shortened in PILO+SE group(P<0.05),but there was no significant difference between PILO+SE group and PILO+5,7-DHT group.Conclusion: Depletion of serotonin may facility the rats’ epileptic seizures,but we could not interpret which may cause epileptic rats’ cognitive deficit.