| Project/Area Number |
04454544
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | KAGOSHIMA UNIVERSITY |
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Principal Investigator |
FUKUDA Takeo KAGOSHIMA UNIVERSITY,PHARMACOLOGY,PROFESSOR, 医学部, 教授 (70038694)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Takao KAGOSHIMA UNIVERSITY,PHARMACOLOGY,INSTRUCTOR, 医学部, 講師 (10041336)
NOMOTO Masahiro KAGOSHIMA UNIVERSITY,PHARMACOLOGY,ASSOCIATE PROFESSOR, 医学部, 助教授 (50208401)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | Parkinsonism / Dopamine D_1 receptor / Dopamine D_2 receptor / Common Marmoset / MPTP / Dopamine / サル / D_1 / D_2 / コモン・マーモセット / ダイアリシス / 線条体 / パーキンソン病 / D・アゴニスト / SKF38393 / SKF82958 / 微小透析法 |
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| Research Abstract |
Adult common marmoset of either sex (age 2 years, weight 280-350g) were treated with MPTP (1-methy1-4-pheny1-1,2,3,6, -tetrahydropyridine) subcutaneously at a dose of 4 mg/kg/week. The animal was administered with sufficient dose of MPTP to render marked parkinsonism for up to 12 months. The cumulative dose of MPTP was 64 to 102 mg/kg/animal. The animal was allowed more than 3 months to recover from the acute effects of MPTP before the start of the experiment. Immediately after the last treatment with MPTP,the marmosets were akinetic and flexed.
The animal showed postural or kinetic tremor of the forelegs during eating. Movement was disorganized and hesitation was obserced upon initiation of every movement. The signs of parkinsonism in the animal did not improve over the period of the experiment. Administration of quinpirole at dosage of 0.1 to 0.3 mg/kg reversed akinesia of animals. Movements were well coordinated and included normal running on the floor of the cage, jumping up to perches or down to the floor. Administration of SKF82958 at dosages of 0.5 to 1.0 mg/kg caused reversal of akinesia and increase in locomotor activity a few minutes after the injection and lasted 60 to 90 minutes. The treatment with CY208243 exhibited reversal of akinesia and increase in locomotor activity at dosage of 0.5 to 1.0 mg/kg. The effects of CY208243 lasted 90 to 120 minutes. During the experiments using SKF82958 and CY208243, animals showed frequent protrusions of the tongue and movements of the lips. When compared for the ability to increase locomotor activity, both drugs induced oral dyskinesia or blinking much more frequent than the D2 dopamine agonist quinpirole. The effects of D1 DA receptor agonists were suppressed completely when the D1 DA receptor antagonist SCH23390 was administered 5 minutes prior to the injection of SKF82958 or CY208243.
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