| Project/Area Number |
15590241
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
TAKEMURA Motohiko Hyogo Col., Med.Fac.Med., Professor, 医学部, 教授 (70207009)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | enzyme / neuroscience / pharmacoloty / gene / neurostimulant / Behavioral sensitization / ヒスタミン / イノシトール / メチルヒスタミン / メチル基転移 / 薬物依存 / エチルアルコール / 不活性化 / メチル基転移酵素 |
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| Research Abstract |
An HPLC system for measurement of histamine and N^T-methylhistamine was constructed as reported by Kasziba et al. with slight modifications. The content of histamine and N^T-methylhistamine in the brain of the rat strain of high ethanol preference (HAP), established by Hishida et al., tended to be larger than those of the rat from low ethanol preference (LAP) strain.When the cortex of HAP was stimulated by histamine in vitro, turnover rate of phosphatidylinositols (PI) was lower than that of LAP. The cortex from mice chronically treated with methamphetamine showed smaller PI turnover rate than that of the control mice. These results suggested that after chronic ethanol or methamphetamine treamtment, activity of histaminergic neurons increases and signal transduction pathway through histamine H_1 receptor-Gq/11-phospholipase C was down-regulated.
It was suggested that histaminergic neuron system plays important role in drug dependence, so several drugs were investigated if they can modify increased locomotion, behavioral sensitization, and stereotypic behavior induced by methamphetamine. Clorgyline, a type A monoamine oxidase inhibitor (MAOI), inhibited hyperlocomotion and behavioral sensitization by methamphetamine. It delayed the onset of stereotypic behavior but this effect was not dose-dependent. Selegiline (a type B MAOI) had no effect on hyperlocomotion but increased stereotypic behavior induced by 2-phenylethylamine.
Knock-out vector of histamine N^T-methyltransferase was constructed and recombinant embryo was acquired.
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