Blocking histamine H1 improves learning and mnemonic dysfunction in mice with social isolation plus repeated methamphetamine injection
Blocking histamine H1 improves learning and mnemonic dysfunction in mice with social isolation plus repeated methamphetamine injection
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DOI：
10.1254/jphs.fp0072424
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发表时间：
2008-06-01
影响因子：
3.5
通讯作者：
Yanai, Kazuhiko
中科院分区：
文献类型：
--
作者：
Jia, Feiyong;Mobarakeh, Jalal Izadi;Yanai, Kazuhiko
本研究旨在探讨组胺H-1和H-3拮抗剂对小鼠学习记忆障碍的影响。使用两种H-1拮抗剂吡拉明和氯氮平，以及典型的H-3拮抗剂硫代巴比妥钠，研究了组胺在社会隔离和反复给药甲基苯丙胺中的作用。与社交隔离小鼠和隔离隔离小鼠相比，社交隔离和重复给予甲基苯丙胺的小鼠表现出明显的脉搏前抑制中断。此外，社会孤立和反复服用甲基苯丙胺会导致显著的学习和记忆功能障碍。氯氮平治疗改善了所有任务中的学习和记忆能力。在除被动回避试验外的所有测试中，吡拉明治疗均能改善测试成绩。然而，硫代巴比妥钠并没有改变学习和记忆能力。多奈哌齐是一种乙酰胆碱酯酶抑制剂，在所有四项任务中都逆转了学习和记忆障碍。目前的研究表明，阻断组胺H-1受体可以改善小鼠的学习和记忆能力，增加了氯氮平或吡拉明治疗某些精神疾病患者(如伴有认知障碍的精神分裂症患者)改善学习和记忆能力的可能性。
The aim of this study was to investigate the effects of histamine H-1 and H-3 antagonists on learning and mnemonic dysfunction in mice. Two H-1 antagonists, pyrilamine and clozapine, and the prototypic H-3 antagonist thioperamide were used to study the role of histamine in mice with social isolation and repeated methamphetamine administration. Mice with social isolation and repeated methamphetamine administration showed significant disruption of prepulse inhibition as compared to both the socially-housed mice and isolation-housing mice. Furthermore, social isolation and repeated methamphetamine administration caused significant learning and mnemonic dysfunctions. Treatment with clozapine improved learning and mnemonic ability in all of the tasks. Pyrilamine treatment ameliorated performance in all the tests examined except for the passive avoidance test. Thioperamide, however, did not change the learning and mnemonic ability. Donepezil, an acetylcholinesterase inhibitor, reversed the learning and mnemonic dysfunction in all four tasks. The present study has shown that blockade of histamine H-1 receptor improved the learning and mnemonic ability in mice, raising the possibility that treatment with clozapine or pyrilamine may improve learning and mnemonic performance in certain patients with psychiatric diseases such as schizophrenic patients with cognitive dysfunction.