| Project/Area Number |
04670161
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
AZUMA Hitoshi Osaka Univ. Medical School Research Associate, 医学部, 助手 (10175870)
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| Co-Investigator(Kenkyū-buntansha) |
YAMATODANI Atsushi Osaka University Medical School Research Associate, 医学部, 助教授 (30116123)
ONO Jiro Osaka University Medical School Research Associate, 医学部, 助手 (20214182)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Histamine / Dopamine / GABA / Catalepsy / Epilepsy / Parkinsonism / Sleep-wakefulness rhythm / Brain microdialysis / 視床下部 / 線条体 / 概日リズム / r-アミノ酪酸 / グルタミン酸 / 結節乳頭核 / 血圧制御 |
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| Research Abstract |
In this project , using a microdialysis techmique, we investigated ihe in vivo dynmics of the central histaminergic system in several pathophysiological states, and obtained following results in Wistar rats. 1. The release of GABA,which is known to be coexisted with histamine in the tuberomammillary histaminergic neurons, from the anterior hypothalamus was evoked by electrical stimulation of the tuberlmammillary mucleus. 2. Glutamate tonically enhanced the release of histamine from the anterior hyphthalamus through NMDA-receptors lacated on presynaptic memgrane as heteroreceptors. 3. Presser response was observed by electrical stimulation of the tuveromammillary mucleus. The effect was abolished by H1-antagonisis. 4. There was a clearcircadian variation of histamine release from both hypothalamus and cerbral cortex, being high during night and low during day time. 5. As an animal model for extrapyramidal disorders such as Parkinsonism, we used a meuroleptic-induced cataleptic behavior in rats and found increase of the release of histamine from the striatum. The histamine release was well-correlated with the cataleptic behavior.
From these findings, we suggested the following phthophysiological sihnificance of the central histaminergic system. 1. Antiepileptic effects of the histaminergic system may mediated partly through co-existing GABA release. 2. Increase of the release of glutamate during epileptic sezure may proveke histamine release through presynaptoc NMDA receptor, which in turn suppress the seizure. 3. The activation of the histaminergic system may function to maintain vigilance. 5. Blockade of dopamine D2-receptors activate the histaminergic system and induced cataleptic behavior. This behavior may be a kind of hyperbigilant state caused by histaminergic activation.
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