| Project/Area Number |
11470199
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Tohoku University |
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Principal Investigator |
ITO Chihiro (2001) Tohoku University, Hospital, Research Associate, 医学部・附属病院, 助手 (60292330)
佐藤 光源 (1999-2000) 東北大学, 大学院・医学系研究科, 教授 (70033321)
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| Co-Investigator(Kenkyū-buntansha) |
KUBOTA Yasuhiko Tohoku University, Hospital, Research Associate, 医学部・附属病院, 助手 (90333799)
OHTSU Hiroshi Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (60250742)
YANAI Kazuhiko Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50192787)
伊藤 千裕 東北大学, 医学部・附属病院, 助手 (60292330)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥15,400,000 (Direct Cost: ¥15,400,000)
Fiscal Year 2001: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | Schizophrenia / Histamine / Knock-out mice / Polymorphism / PET / 覚醒剤精神病 / 逆耐性現象 / メタンフェタミン |
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| Research Abstract |
Schizophrenia resistant to the treatments with D2 antagonists is supposed to have the possible changes of extradopaminergic systems. Meanwhile, histamine was recently suggested to be a neurotransmitter in the mammalian brains, which regulates many brain functions. We have recently found the interesting results about the role of brain histamine on schizophrenia in basic and clinical studies. Methamphetamine-induced behavioral sensitization, which has been well established as the animal model of schizophrenia, induced the enhanced histamine turnover and histamine H1 and H2 receptor mRNA. Behavioral sensitization was also rapidly completed in the histidine decarboxylase deficient mice and both the H1 and H2 receptors deficient mice than in the wild typed mice. In clinical studies, the levels of N-tele-methylhistamine, a major brain HA metabolite, were elevated in the cerebrospinal fluid of schizophrenics. Moreover, the H1 receptor gene variant was related to schizophrenia, and H1 receptor binding sites decreased in schizophrenics. Therefore, the dysfunction of HA neuron system may participate in the extradopaminergic brain dysfunction of schizophrenia, and HA agents may improve the refractory schizophrenia.
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