| Project/Area Number |
16300123
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
HAYAISHI Osamu Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Researcher, 分子行動生物学部門, 研究員 (40025507)
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| Co-Investigator(Kenkyū-buntansha) |
URADE Yoshihiro Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Head, 分子行動生物学部門, 研究部長 (10201360)
HUANG Zhi-Li Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Vice Head, 分子行動生物学部門, 研究副部長 (10321704)
江口 直美 (財)大阪バイオサイエンス研究所, 分子行動生物学部門, 研究副部長 (10250086)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2004: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | Wakefulness / Brief awakening / Gene knockout mice / Histamine / TMN / GABA / A_<2A> receptor / Caffeine / Wakefulness / Brief awakeming / Gene knockout mice / Histamine / TMN / GABA / A2A receptor |
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| Research Abstract |
Under baseline conditions, gene knockout (KO) mice for histamine H_1 receptors (H_1R) showed sleep-wake cycles essentially identical to those of wild-type (WT) mice but with fewer incidents of brief awakening (<16-sec epoch) during non-rapid eye movement (NREM) sleep and a shorter latency for initiating NREM sleep after an i.p. injection of saline. The H_1R antagonist, pyrilamine, mimicked these effects in WT mice. A histamine H_3 receptor antagonist, ciproxifan, increased wakefulness in WT mice after an i.p. injection in a dose-dependent manner but not at all in H_1R KO mice, although the histamine release from the frontal cortex was increased in both genotypes of mice. These results indicate that H_1R is involved in the regulation of state transitions from NREM sleep to wakefulness and that the arousal effect of the H_3 antagonist completely depends on the activation of histaminergic system through H_1R.
Administration of an adenosine A_<2A> receptor (A_<2A>R) agonist, CGS21680, to th
… More
e rat basal forebrain inhibited both wakefulness and the histamine release in the frontal cortex. Microdialysis studies with anesthetized rats revealed that the A_<2A>R-agonist administration inhibited the histamine release in the cortex and increased the GABA release in the histaminergic tuberomammillary nucleus (TMN) but not in the cortex. The A_<2A>R-agonist-induced inhibition of the histamine release was reversed by the administration of GABA antagonist, picrotoxin, into the TMN, indicating that the GABAergic inhibition of TMN was involved in the inhibition of wakefulness by A_<2A>R agonist. Caffeine is the most popular substance to induce wakefulness but the receptor subtype involved in the caffeine-induced wakefulness remained unclear. When we administrated caffeine in WT, adenosine A_1 receptor (A_1R)-KO, and A_<2A>R-KO mice, caffeine induced wakefulness in WT and A_1R-KO mice but not at all in A_<2A>R-KO mice, indicating that the arousal effect of caffeine completely depends on A_<2A>R, but not A_1R. Less
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