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Change of dopamine and serotonin metabolism, and NMDA-type glutamate receptors in the brain of Parkinson's disease

Research Project

Project/Area Number 12670586
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionHirosaki University

Principal Investigator

MATSUNAGA Muneo  Hirosaki University School of Medicine, Professor, 医学部, 教授 (80003599)

Co-Investigator(Kenkyū-buntansha) TOMIYAMA Masahiko  Hirosaki University School of Medicine, Assistant, 医学部, 助手 (40311542)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywords6-OH model rat / dyskinesia / motor sensitization / GABAergic neuron / 5-HT agonist / glutamic acid decarboxylase / pallidotomy / subthalamic nucleus stimulation / セロトニンニューロン / ドパミン代謝 / NMDA型グルタミン酸受容体 / In vivo microdialysis / In situ hybridization / レボドパ / in vivo microdialysis / in situ hybridization
Research Abstract

To determine the effects of a 5-hydroxytryptamine (5-HT)_<1A> agonist, 8-OH-DPAT, on behavioral sensitization induced by intermittent administration of levodopa in 6-hydroxydopamine (6-OHDA) rats, we elucidated rotational behavior and messenger RNAs coding prodynorphin (DYN) and glutamic acid decarboxylase (GAD) in the dopamine-denervated striatum of 6-OHDA-lesioned rats which repeatedly received either saline or levodopa or 8-OH-DPAT plus levodopa twice a day for two weeks. Rotational behavior was markedly increased in 6-OHDA-lesioned rats treated with intermittent levodopa. However, coadministration of 8-OH-DPAT with levodopa attenuated the increase of circulation behavior. Expression of GAD and DYN mRNAs was significantly increased in the dopamine denervated striatum of 6-OHDA-lesioned rats after intermittent levodopa treatment, whereas additional 8-OH-DPAT administration significantly suppressed increases of their expression. These results suggest that 5-HT_<1A> receptor agonists can alleviate levodopa-induced motor complications in Parkinson's disease.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 木村 珠喜, 古澤 健一, 松永 宗雄 ほか: "Levodopa投与によって生じる運動合併症に対するセロトニン(5HT)1A受容体アゴニスト、8=OH-DPATの効果"弘前医学. 53巻1号. 17-25 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 神成 一哉, 倉橋 幸造, 松永 宗雄 ほか: "選択的5-HT受容体アゴニスト、クエン酸タンドスピロンのL-DOPA-induced dyskinesiaの軽減効果"脳と神経. 54巻2号. 133-137 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishie M, Yoshida Y, Hirata Y, Matsunaga M: "Generation of symptomatic palatal tremor is not correlated with inferior olivary Hypertrophy"Brain. 126. 1348-1357 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomiyama M. Kimura T, Maeda T, Tanaka H, Furusawa K, Matsunaga M: "expression of metabotropic glutamate receptor mRNAs in the human spinal cord"J Neurol Sci. 189. 65-69 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kimura T, Furusawa K, Matsunaga M, Tomiyama M, Tanaka H, Kannari K: "Effects of 8-OH-DPAT, a 5-HT1A receptor agonist, on L-DOPA-induced motor complication in 6-hydroxydopamine-lesioned rats"Hirosaki Med J. 53. 17-25 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kannari K, Yamato H, Shen H, Tomiyama M, Suda T, Matsunaga M: "Activation of 5-HT1A but not 5-HT1B receptors attenuates an increase in extracellular dopamine derived from exogeneously administrated L-DOPA in the striatum with nigrostriatal denervation"J Neurochem. 76. 1346-1353 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamato H, Kannari K, Shen H, Suda T, Matsunaga M: "Fluoxetine reduces L-DOPA-derived extracellular DA in the 6-OHDA-lesioned rat striatum"Neuro Report. 12. 1123-1126 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kannari K, Kurahashi K, Tomiyama M, Maeda T, Arai A, Baba M, Matsunaga M: "Tandospirone citrate, a selective 5-HT1A agonist, alleviates L-DOPA-induced dyskinesia in patient with Parkinson disease"Brain & Nerve. 133-137 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shen H, Kannari K, Yamato H, Arai A, Matsunaga M: "Effects of benserazide on L-DOPA-derived extracellular dopamine levels and an aromatic L-amino acid decarboxylase activity in the striatum of 6-hydroxydopamine-lesioned rats"Tohoku J Exp Med. 199. 149-159 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 木村 珠喜, 古澤 健一, 松永 宗雄ほか: "Levodopa投与によって生じる運動合併症に対するセロトニン(5HT)1A受容体アゴニスト、8=OH-DPATの効果"弘前医学. 53巻1号. 17-25 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 神成 一哉, 倉橋 幸造, 松永 宗雄ほか: "選択的5-HT受容体アゴニスト、クエン酸タンドスピロンのL-DOPA-induced dyskinesiaの軽減効果"脳と神経. 54巻2号. 133-137 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishie M, Yoshida Y, Hirata Y, Matsunaga M.: "Generation of symptomatic palatal tremor is not correlated with inferior olivary Hypertrophy"Brain. 126. 1348-1357 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Tomiyama, T.Kimura, M., Matsunaga et al.: "Expression of metabotropic glutamate receptor mRNAs in the human spinal cord : Inplications for selective vulnerability of spinal motor neurons in ALS"J. Neurol. Sci.. 189. 65-69 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Yamato, K.Kannari, M.Matsunaga et al.: "Fluoxetine reduces L-DOPA-derived extracellular DA in the 6-OHDA-lesioned rat striatum"NeuroReporta. 12. 1123-1126 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Kannari, H.Yamato, M.Matsunaga et al.: "Activation of 5-HT1A but not 5-HT1B receptors attenuates an increase in extracellular dopamine derived from exogenously administered L-DOPA in the striatum with nigrostriatal denervation"J. Neurochem.. 76. 1346-1353 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Tomiyama, T.Kimura, M.Matsunaga et al.: "Molecular Mechanism & Therapeutics of ALS"Expression of mRNAs coding metabotropic glutamate receptor and their slice variants in the human spinal cord. 217-222 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Kimura,M.Tomiyama,M.Matsunaga, et al.: "Expression of the adenosine A2A receptor mRNA in the rat striatum : Increase by nigrostriatal denervation and L-DOPA treatment."Movement Disorder. 15;supple3. 29 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Kannari,M.Tomiyama,M.Matsunaga, et al.: "Reserpine pretreatment prevents increases in extracellular striatal dopamine following L-DOPA administration in rats with nigrostriatal denervation."J.Neurochem.. 74. 263-269 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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