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Molecular mechanisms of drug dependency and stimulant psychosis induced by methamphetamine

Research Project

Project/Area Number 15390080
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionOsaka University

Principal Investigator

MIKI Naomasa  Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (40094445)

Co-Investigator(Kenkyū-buntansha) TAIRA Eiichi  Iwate Medical School, Professor, 医学部, 教授 (60263240)
KUO Che-hui  Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (50126570)
TANAKA Hidekazu  Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70273638)
IRIE Yasuyuki  Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70303948)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 2004: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2003: ¥11,100,000 (Direct Cost: ¥11,100,000)
Keywordsmethamphetamine / gene expression Arc / Arcadline / N-cadherin / MAP2 / synaptic remodeling / stimulant psychosis / methamphetamine / Arcadline / synaptic remodeling / stimulant psychosis / 精神依存 / Arc / シナプス / 樹状突起
Research Abstract

We hypothesizes that drug dependency and stimulant psychosis induced by methamphetamine are triggered by gene expression which causes remodeling of the synapses in the nucleus accumbens. We analyzed the functions of Arc and Arcadline which are induced by methamphetamine.
1)Arcadlin : Neural activity induces structural changes of synapse in which the cell adhesion molecules participate. We found that synapses were expanded laterally in 30 minutes after depolarization. N-cadherin participated in expansion of synapse adhesion plane. Moreover, both AMPA receptor and polymerization of actin are necessary.
On the other hand, Arcadlin is a cadherin family and induced by neural activity. We found that Arcadlin formed a complex with N-cadherin and was internalized, and then the number of synapses decreased. Conversely, the neurons from Arcadlin knockout mice increased the number of synapses.
2)Arc : Arc is an immediate early gene induced by methamphetamine and its mRNA is carried to the dendrite to synthesize the protein. It was found that the immunoreactivity of MAP2 was markedly decreased by overexpression of Arc. When the electric shock convulsive seizure was applied to mice, immunostaining of Arc was increased in the granular layer and that of MAP was significantly decreased.
From these data, Arcadline and Arc which are induced by methamphetamine associate with other proteins to change the synaptic morphology and functions, which may cause drug dependence and stimulant psychosis.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (22 results)

All 2005 2004 2003 Other

All Journal Article (19 results) Publications (3 results)

  • [Journal Article] Concomitant translocation of Purα with its (PurBPs) from nuclei to cytoplasm during binding proteins neuronal development.2005

    • Author(s)
      L-H.Zen, et al.
    • Journal Title

      Neurosci.Res. 51

      Pages: 105-109

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Concomitant translocation of Purα with Its (PurBPs) from nuclei to cytoplasm during binding proteins neuronal development.2005

    • Author(s)
      L-H.Zen, K.Okamura, H.Tanaka, N.Miki, C-H.Kuo
    • Journal Title

      Neurosci.Res. 51

      Pages: 105-109

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Concomitant translocation of Purα with its binding proteins (PurBPs) from nuclei to cytoplasm during neuronal development.2005

    • Author(s)
      L-H.Zen, K.Okamura, H.Tanaka, N.Miki, C-H.Kuo
    • Journal Title

      Neurosci.Res. 51

      Pages: 105-109

    • NAID

      10015450609

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Characterization of novel Purα-binding proteins in mouse brain.2004

    • Author(s)
      L-H.Zeng, et al.
    • Journal Title

      Neurochem.Int. 45

      Pages: 753-7538

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Arc interacts with microtubule/MAP2 (microtubule-associated protein 2) and attenuates MAP2 immunoreactivity in the dendrites.2004

    • Author(s)
      T.Fujimoto, et al.
    • Journal Title

      J.Neurosci.Res. 76

      Pages: 51-63

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cadherin activity is required for activity-induced spine remodeling.2004

    • Author(s)
      K.Okamura, et al.
    • Journal Title

      J.Cell Biol. 167

      Pages: 961-972

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Characterization of novel Purα-binding proteins in mouse brain.2004

    • Author(s)
      L-H.Zeng, T.Fujimoto, E.Kumamaru, Y.Irie, N.Miki, C-H.Kuo
    • Journal Title

      Neurochem.Int. 45

      Pages: 753-758

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Arc interacts with microtubule/MAP2 (microtubule-associated protein 2) and attenuates MAP2 immunoreactivity in the dendrites.2004

    • Author(s)
      T.Fujimoto, H.Tanaka, E.Kumamaru, K.Okamura, N.Miki
    • Journal Title

      J.Neuroscie.Res. 76

      Pages: 51-63

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cadherin activity is required for activity-induced spine remodeling.2004

    • Author(s)
      K.Okamura, H.Tanaka, Y.Yagita, L-H.Zeng, D.R.Colman, N.Miki
    • Journal Title

      J.Cell Biol. 167

      Pages: 961-972

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Characterization of novel Purα-binding proteins in mouse brain.2004

    • Author(s)
      L-H.Zeng, T.Fujimoto, E.Kumamaru, Y.Irie, N.Miki外
    • Journal Title

      Neurochem.Int. 45

      Pages: 753-758

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Arc interacts with microtubule/MAP2(microtubule-associated protein 2) and attenuates MAP2 immuno-reactivity in the dendrites.2004

    • Author(s)
      T.Fujimoto, H.Tanaka, E.kumamaru, K.Okamura外
    • Journal Title

      J.Neuroscie.Res. 76

      Pages: 51-63

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cadherin activity is required for activity-induced spine remodeling.2004

    • Author(s)
      K.Okamura, H.Tanaka, L-H.Zeng, D.R.Colman, N.Miki
    • Journal Title

      J.Cell Biol. 167

      Pages: 961-972

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The accumulation of Arc (an immediate early gene) mRNA by the inhibition of protein synthesis.2003

    • Author(s)
      H.Ichikawa, et al.
    • Journal Title

      J.Pharmacol.Sci. 91

      Pages: 247-254

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular cloning and characterization of rKAB1, which interacts With KARP-1, localizes in the nucleus and protects cell against oxidative death.2003

    • Author(s)
      E.Do, et al.
    • Journal Title

      Mol.Cell.Biochem. 248

      Pages: 77-83

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Arrest of cell cycle by Amida which is phosphorylated by Cdc2 kinase.2003

    • Author(s)
      Y.Gan, et al.
    • Journal Title

      Mol.Cell.Biochem. 246

      Pages: 179-185

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The accumulation of Arc (an immediate early gene) mRNA by the inhibition of protein synthesis.2003

    • Author(s)
      H.Ichikawa, T.Fujimoto, E.Taira, N.Miki
    • Journal Title

      J.Pharmacol.Sci. 91

      Pages: 247-254

    • NAID

      130000073706

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Molecular cloning and characterization of rKAB1, which interacts with KARP-1, localizes in the nucleus and protects cells against oxidative death.2003

    • Author(s)
      E.Do, E.Taira, Y.Irie, Y.Gan, H.Tanaka, C-H.Kuo, N.Miki
    • Journal Title

      Mol.Cell.Biochem. 248

      Pages: 77-83

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Arrest of cell cycle by Amida which is phosphorylated by Cdc2 kinase.2003

    • Author(s)
      Y.Gan, E.Taira, Y.Irie, T.Fujimoto, N.Miki
    • Journal Title

      Mol.Cell.Biochem. 246

      Pages: 179-185

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] The accumulation of Arc( an immediate early gene) mRNA by the inhibition of protein synthesis.2003

    • Author(s)
      H.Ichikawa, T.Fujimoto, E.Taira, N.Miki
    • Journal Title

      J.Pharmacol.Sci. 91

      Pages: 247-254

    • NAID

      130000073706

    • Related Report
      2004 Annual Research Report
  • [Publications] T.Fujimoto, H.Tanaka, E.Kumamaru, N.Miki et al.: "Arc interacts with microtubule/MAP2 (microtubule-associated protein 2) and attenuates MAP2 immunoreactivity in the dendrites"J.Neurosci.Res.. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] G.Phillips^*, H.Tanaka, et al.: "Gamma-protocadherins are targeted to subsets of synapses and intracellular organelles in neurons"J.Neurosci.. 23. 5096-5104 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] H.Ichikawa, T.Fujimoto, E.Taira, N.Miki: "The accumulation of Arc (an immediate early gene) mRNA by the inhibition of protein synthesis"J.Pharmacol.sci.. 91. 247-254 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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