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2005 Fiscal Year Final Research Report Summary

Neurochemical and pharmaco-behavioural studies on the biological basis of oral dyskinesia

Research Project

Project/Area Number 16591897
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionNihon University

Principal Investigator

SAIGUSA Tadashi  Nihon University, School of Dentistry, Lecture, 歯学部, 講師 (50277456)

Co-Investigator(Kenkyū-buntansha) KOSHIKAWA Noriaki  Nihon University, School of Dentistry, Professor, 歯学部, 教授 (80130491)
TOMIYAMA Katsunori  Nihon University, Advanced Research Institute for the Science and Humanities, Associate Professor, 大学院・総合科学研究科, 助教授 (40197942)
IKEDA Hiroko  Nihon University, School of Dentistry, Research Assistant, 歯学部, 助手 (70297844)
Project Period (FY) 2004 – 2005
KeywordsOral dyskinesia / Dopamine / Dexamphetamine / Endomorphin-1 / Endomorphin-2 / Nucleus accumbens / Striatum / Rat
Research Abstract

1.Oral dyskinesia is a neurological syndrome associated with aging or use of neuroleptics and drugs for Parkinson's disease. It is characterized by repetitive stereotyped oral movement. The detailed pathophysiological basis of the disorder remains unclear, but behavioural studies suggest the significance of increase in dopamine (DA) function in the striatum and nucleus accumbens for the production of repetitive jaw movements of rats. In order to investigate the biological basis of the enhancement of DA function, we focused on the mechanisms of action of (1)the intrastriatal injection of dexamphetamine on the striatal DA efflux, (2)the intraaccumbal infusion of the putative delta receptor agonist TAN-67 on the accumbal DA efflux, (3)the intraaccumbal infusion of endomorphin (EM)-2 and EM-1, the endogenous mu receptor agonists on the accumbal DA efflux and (4)the local infusion of alpha-methyl-p-tyrosine (AMPT), a tyrosine hydroxylase inhibitor on the striatal and accumbal DA efflux. The DA levels were monitored by in vivo brain microdialysis.
2.The present study reveals that (1)both vesicular and cytosolic DA pools contribute to the intrastriatal injection of dexamphetamine-induced striatal DA efflux. (2)(-)-TAN-67 can generate a burst of free radicals that trigger glutamate release which ultimately activates NMDA receptors that enhance the accumbal DA levels. (3)The intraaccumbal infusion of EM-2 and EM-1 increase accumbal DA efflux by mechanisms that differ. Thus, the effects of EM-2 are not mediated via opioid receptors in contrast to the effects of EM-1 that are mediated via mu1-opioid receptors. (4)The local infusion of AMPT is a valuable tool for analyzing the role of AMPT-sensitive DA pools within a particular brain area, but it cannot be used to compare effects across different brain structures, since a fixed dose of AMPT differentially affects the nucleus accumbens and dorsal striatum.

  • Research Products

    (7 results)

All 2006 2005

All Journal Article (7 results)

  • [Journal Article] Endomorphin-2 and Endomorphin-1 Promote the Extracellular Amount of Accumbal Dopamine via Non-Opioid and Mu-Opioid Receptors, Respectively2006

    • Author(s)
      Okutsu et al.
    • Journal Title

      Neuropsychopharmacology 31

      Pages: 375-383

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The non-peptidic delta opioid receptor agonist TAN-67 dopamine efflux in the nucleus accumbens of freely moving rats via a mechanism that involves both glutamate and free radicals2005

    • Author(s)
      Fusa et al.
    • Journal Title

      Neuroscience 130

      Pages: 743-753

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Contribution of vesicular and cytosolic dopamine to the transient increased striatal dopamine efflux after intrastriatal application of dexamphetamine2005

    • Author(s)
      Watanabe et al.
    • Journal Title

      Neuroscience 136

      Pages: 251-257

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effects of alpha-methyl-p-tyrosine on the extracellular dopamine levels in the nucleus accumbens and the dorsal striatum of freely moving rats2005

    • Author(s)
      Watanabe et al.
    • Journal Title

      Journal of Oral Science 47

      Pages: 185-190

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The non-peptidic delta opioid receptor agonist TAN-67 enhances dopamine efflux in the nucleus accumbens of freely moving rats via a mechanism that involves both glutamate and free radicals2005

    • Author(s)
      Fusa et al.
    • Journal Title

      Neuroscience 130(3)

      Pages: 743-753

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Contribution of vesicular and cytosolic dopamine to the transient increased striatal dopamine efflux after intrastriatal application of dexamphetamine2005

    • Author(s)
      Watanabe et al.
    • Journal Title

      Neuroscience 136(1)

      Pages: 251-257

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effects of alpha-methyl-p-tyrosine on the extracellular dopamine levels in the nucleus accumbens and the dorsal striatum of freely moving rats2005

    • Author(s)
      Watanabe et al.
    • Journal Title

      Journal of Oral Science 47(4)

      Pages: 185-190

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2007-12-13  

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