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J Zhejiang Univ (Med Sci)  2017, Vol. 46 Issue (1): 1-6    DOI: 10.3785/j.issn.1008-9292.2017.02.01
    
Mechanisms of histamine ameliorating memory impairment induced by pentylenetetrazole-kindling epilepsy in rats
ZHANG Lisan(),CHEN Guanfeng,CHEN Jiefang,HE Xudong,HU Xingyue()
Department of Neurology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
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Abstract  Objective

To investigate the effects of neuronal histamine on spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and to explore its mechanisms.

Methods

A subconvulsive dose of pentylenetetrazole (35 mg/kg) was intraperitoneally injected in rats every 48 h to induce chemical kindling until fully kindled. Morris water maze was used to measure the spatial memory acquisition of the rats one week after fully pentylenetetrazole-kindled, and the histamine contents in different brain areas were measured spectrofluorometrically. Different dosages of hitidine (the precursor of histamine), pyrilamine (H1 receptor antagonist), and zolantidine (H2 receptor antagonist) were intraperitoneally injected, and their effects on spatial memory acquisition of the rats were observed.

Results

Compared with control group, escape latencies were significantly prolonged on Morris water maze training day 2 and day 3 in pentylenetetrazole-kindling epilepsy rats (all P < 0.05); and the histamine contents in hippocampus, thalamus and hypothalamus were decreased significantly (all P < 0.05). Escape latencies were markedly shortened on day 3 by intraperitoneally injected with histidine 500 mg/kg, and on day 2 and day 3 by intraperitoneally injected with histidine 1000 mg/kg in pentylenetetrazole-kindling epilepsy rats (all P < 0.05). The protection of histidine was reversed by zolantidine (10 and 20 mg/kg), but not by pyrilamine.

Conclusion

Neuronal histamine can improve the spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and the activation of H2 receptors is possibly involved in the protective effects of histamine.



Key wordsEpilepsy/physiopathology      Epilepsy/chemically induced      Histamine/pharmacology      Pentylenetetrazole/toxicity      Memory disorders/drug therapy      Maze learning      Disease models, animal     
Received: 02 October 2016      Published: 06 July 2017
CLC:  R742.1  
  R965  
Corresponding Authors: HU Xingyue     E-mail: zls09@zju.edu.cn;huxingyue2003@126.com
About author: HU Xingyue. E-mail: huxingyue2003@126.com
Cite this article:

ZHANG Lisan,CHEN Guanfeng,CHEN Jiefang,HE Xudong,HU Xingyue. Mechanisms of histamine ameliorating memory impairment induced by pentylenetetrazole-kindling epilepsy in rats. J Zhejiang Univ (Med Sci), 2017, 46(1): 1-6.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2017.02.01     OR     http://www.zjujournals.com/med/Y2017/V46/I1/1


组胺改善癫痫所致记忆形成障碍的实验研究

目的

研究脑内组胺是否能改善戊四唑诱导癫痫大鼠的空间记忆形成障碍,并探讨其可能的作用机制。

方法

采用腹腔注射亚惊厥剂量(35 mg/kg)的戊四唑建立SD大鼠癫痫模型。建模一周后,用Morris水迷宫实验测定大鼠的空间记忆形成能力,并采用化学荧光法测定大鼠脑组织中组胺的含量。腹腔内注射不同剂量的组胺酸、组胺H1受体拮抗剂吡拉明或组胺H2受体拮抗剂卓兰替丁,观察它们对癫痫大鼠空间记忆形成的影响。

结果

与对照组比较,模型组大鼠训练第二、三天逃脱潜伏期均延长(均P < 0.05);海马、丘脑和下丘脑组胺含量均下降(均P < 0.05)。与癫痫模型组比较,腹腔注射500 mg/kg组氨酸可缩短水迷宫训练第三天的逃脱潜伏期(P < 0.05);腹腔注射1000 mg/kg组氨酸可缩短水迷宫训练第二、三天的逃脱潜伏期(均P < 0.05)。与腹腔注射1000 mg/kg组氨酸的大鼠比较,各剂量的吡拉明均不影响组氨酸改善大鼠空间记忆形成障碍的作用(均P>0.05);而腹腔注射10 mg/kg或20 mg/kg卓兰替丁可延长大鼠水迷宫训练第二、三天的逃脱潜伏期(均P < 0.05)。

结论

脑内组胺能改善戊四唑诱导癫痫大鼠的空间记忆形成障碍,其作用可能与组胺H2受体激活有关。


关键词: 癫痫/病理生理学,  癫痫/化学诱导,  组胺/药理学,  戊四唑/毒性,  记忆障碍/药物疗法,  迷宫学习,  疾病模型, 动物 
($\overline {x}$±s, ng/g)
与对照组比较,*P<0.05.
组别n皮质海马下丘脑丘脑
对照组1048.1±6.848.1±7.7817.5±26.3328.6±31.6
模型组1037.5±5.914.9±2.3*430.1±13.7*146.1±35.1*
Tab 1 Changes of histamine content of different brain area of PTZ-kindling epilepsy in rats
Fig 1 Protective effects of histidine on spatial memory deficit induced by PTZ-kindling epilepsy in rats (n=10 for each group)
Fig 2 Influence of pyrilamine, a H1 receptor antagonist, on protection of spatial memory impairment induced by histidine (n=10 for each group)
Fig 3 Influence of zolantidine, a H2 receptor antagonist, on protection of spatial memory impairment induced by histidine (n=10 for each group)
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