Effects of histamine H3 antagonists and donepezil on learning and mnemonic deficits induced by pentylenetetrazol kindling in weanling mice
Effects of histamine H3 antagonists and donepezil on learning and mnemonic deficits induced by pentylenetetrazol kindling in weanling mice
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DOI：
10.1016/j.neuropharm.2005.09.017
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发表时间：
2006-03-01
影响因子：
4.7
通讯作者：
Yanai, K
中科院分区：
文献类型：
--
作者：
Jia, FY;Kato, M;Yanai, K
儿童癫痫是其主要的危险因素之一，涉及认知和行为的各种问题。戊四氮（PTZ）点燃是目前公认的癫痫研究模型。本研究的目的是阐明发育中小鼠PTZ点燃的学习和记忆特征，并检查硫代哌丁胺和JNJ-5207852（两种组胺H-3受体拮抗剂）和多奈哌齐（一种乙酰胆碱酯酶（AChE）抑制剂）对发育中小鼠脑中PTZ点燃诱导的学习和记忆缺陷的影响。PTZ点燃导致学习和记忆缺陷的社会歧视，声学恐惧条件反射，水迷宫和被动回避测试进行评估。除水迷宫试验外，硫代哌丁胺和JNJ-5207852可改善所有试验中PTZ点燃诱导的学习和记忆缺陷。此外，在所有测试中，多奈哌齐均显著改善PTZ点燃诱导的学习和记忆障碍。这些结果表明，组胺和乙酰胆碱参与不同的过程中的学习和记忆在大脑和组胺H-3受体拮抗剂可能是有用的，在治疗癫痫的认知障碍。(c)2005爱思唯尔有限公司保留所有权利。
Childhood epilepsy is one of the main risk factors for it variety of problems involving cognition and behavior. Pentylenetetrazol (PTZ) kindling is currently an acceptable model for epilepsy research. The objectives of this Study are to clarify the learning and mnemonic characteristics of PTZ kindling in developing mice, and to examine the effects of thioperamide and JNJ-5207852, two histamine H-3 receptor antagonists and donepezil, an acetylcholinesterase (AChE) inhibitor, on learning and memory deficits induced by PTZ kindling in the brains of developing mice. PTZ kindling led to learning and mnemonic deficits as assessed by social discrimination, acoustic fear conditioning, water maze and passive avoidance tests. Thioperamide and JNJ-5207852, ameliorated PTZ kindling-induced learning and mnemonic deficits in all tests except for the water maze test. In addition, the learning and mnemonic impairments induced by PTZ kindling were significantly improved by donepezil in all tests. These findings Suggest that histamine and acetylcholine are involved in the different processes of learning and memory in the brain and that histamine H-3 receptor antagonists might be useful in the treatment of cognitive impairment in epilepsy. (c) 2005 Elsevier Ltd. All rights reserved.