| Project/Area Number |
60570501
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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 |
Psychiatric science
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| Research Institution | TOHOKU UNIVERSITY (1986)
Okayama University (1985) |
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Principal Investigator |
SATO Mitsumoto Professor, Tohoku University Medical School, 工学部, 教授 (70033321)
|
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| Co-Investigator(Kenkyū-buntansha) |
風早 靖子 岡山大学, 医学部附属病院, 医員
AKIYAMA Kazufumi Assistant Staff, Okayama University Medical School, 医学部附属病院, 助手 (40150990)
KASAHAYA Yasuko Medical Staff, Okayama University Medical School
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1986: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1985: ¥1,000,000 (Direct Cost: ¥1,000,000)
|
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| Keywords | Anti-psychotics / striatum / dopamine metabolism / ドパミン受容体 |
|---|
| Research Abstract |
The after-effect of intermittent and continuous treatment of haloperidol on the dopaminergic system in rat brain were examined in this project. Each rat was treated for 14 days with either a single daily intra-peritoneal injection of haloperidol (intermittent haloperidol group, I-H group) or with a subcutaneously implanted pump that released haloperidol for 14 days ( continuous haloperidol group, C-H group). On the 7th day after cessation of injections or removal of pumps, the changes in dopamine metabolism, dopamine receptors and carbachol, norepinephrine and serotonin stimulated phosphatidylinositol(PI) turnover were studied. Behaviorally, the rats of C-H group showed significantly less sensitivity to a challenge dose of apomorphine than those of L-H group. Increase in striatal dopamine metabolites (DOPAC, HVA) with slight decrease in dopamine to a test dose of haloperidol was significantly less in the C-H group than the I-H group, while the opposite change was found in (3H)-spiperon binding sites of the striatum. However, neither the basal nor the stimulated level of PI turnover changed significantly in these two groups. It is concluded that continuously administered haloperidol exerts a stronger effect on striatal dopamine transmission, which in turn produces a greater tolerance to an acute dose of haloperidol than intermittent haloperidol administration probably due to increased dopamine receptor sites.
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