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EFFECTS OF D_1 DOPAMINE RECEPTOR AGONIST ON MPTP-TREATED PARKINSON-MODEL IN COMMON MARMOSET.

Research Project

Project/Area Number 04454544
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 応用薬理学・医療系薬学
Research InstitutionKAGOSHIMA UNIVERSITY

Principal Investigator

FUKUDA Takeo  KAGOSHIMA UNIVERSITY,PHARMACOLOGY,PROFESSOR, 医学部, 教授 (70038694)

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)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
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)
KeywordsParkinsonism / 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
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.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] M.Nomoto and T.Fukuda: "A selective MAO B inhibitor Rol9-6327 potentiates the effects of levodopa on parkinsonism induced by MPTP in the common marmoset." Neuropharmacology. 32. 473-477 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Nomoto and T.Fukuda: "The effects of D1 and D2 dopamine receptor agonist and antagonist on parkinsonism in chronic MPTP-treated monkeys." Advances in Neurology. 60. 119-122 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Nomoto,M.Irifune,K.Fukuzaki and T.fukuda: "Effects of bifemelane on parkinsonism induced by 1-methy1-4-pheny1-1,2,3,6-tetrahydropyridine(MPTP)in the common marmoset." Neuroscience Letters. 178. 95-98 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Irifune,M.Nomoto and T.Fukuda: "Effects of talipexole on motor behavior in normal and MPTP-treated common marmoset." European J.Pharmacology. 238. 235-240 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Nomoto and T.Fukuida: "A selective MAO B inhibitor Ro19-6327 potentiates the effects of levodopa on parkinsonism induced by MPTP in the common marmoset." Neuropharmacology. 32. 473-477 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Nomoto and T.Fukuda: "The effects of D_1 and D_2 dopamine receptor agonist and antagonist on parkinsonism in chronic MPTP-treated monkeys." Advance in Neurology. 60. 119-122 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Nomoto, M.Irifune, K.Fukuzaki and T.Fukuda: "Effects of bifemelane on parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the common marmoset." Neuroscience Letters. 178. 95-98 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Irifune, M.Nomoto and T.Fukuda: "Effects of talipexole on motor behavior in normal and MPTP-treated common marmoset." European J.Pharmacol.238. 235-240 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.Nomoto and T.Fukuda: "A selective MAO B inhibitor Ro19-6327 potentiates the effects of levodopa on parkinsonism induced by MPTP in the common marmoset" Neuropharmacoloqy. 32. 473-477 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Nomoto and T.Fukuda: "The effects of D1 and D2 dopamine receptor agonist and antagonist on parkinsonism in chronic MPTP-treated monkeys" Advances in Neurology. 60. 119-122 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Nomoto,M.Irifune,K.Fukuzaki and T.Fukuda: "Effects of bifemelane on parkinsonism.induced by 1-methy1-4-pheny1-1,2,3,6-tetrahydropyridine(MPTP) in the common marmoset" Neuroscience Letters. 178. 95-98 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Irifune,M.Nomoto,and T.Fukuda: "Effects of talipexole on motor behavior in normal and MPTP-treated common marmoset" European J.Pharmacology. 238. 235-240 (1993)

    • Related Report
      1994 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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