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1993 Fiscal Year Final Research Report Summary

Lasting alterations in drug biodistribution in the animal brain regions after repeated administration of methamphetamine or cocaine

Research Project

Project/Area Number 04670687
Research Category

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

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionTohoku University

Principal Investigator

MATSUOKA Hiroo  Tohoku University Hospital, Department of Psychiatry, Assistant, 医学部・附属病院, 助手 (00173815)

Co-Investigator(Kenkyū-buntansha) YOSHIDA Sumiko  Tohoku University Hospital, Department of Psychiatry, Staff psychiatrist, 医学部・附属病院, 医員
NUMACHI Yohtaro  Tohoku University Hospital, Department of Psychiatry, Assistant, 医学部・附属病院, 助手
INNOSAKA Takao  Tohoku University Hospital, Department of Psychiatry, Assistant, 医学部・附属病院, 助手
SATO Mitsumoto  Tohoku University School of Medicine, Department of Psychiatry, Professor, 医学部, 教授 (70033321)
Project Period (FY) 1992 – 1993
KeywordsAnimal models for schizophrenia / Brain distribution / Central stimulants / Cocaine / Dopamine transporter / Methamphetamine psychosis / Releasing amines / Reverse tolerance phenomenon
Research Abstract

In animals, a long-term behavioral sensitization to methamphetamine (MAP) has been confirmed after chronic MAP (reverse tolerance phenomenon). To date, it is suggested that lasting enhancemnt of MAP-induced increase in dopamine (DA) release in the striatum and nucleus accumbens relates to induction and manifestation of the brain vulnerability to psychotic relapses. According to the exchange diffusion model (Fischer and Cho, 1979) regarding the MAP-induced release of DA at nerve terminals, it seems possible to provide a working hypothesis that that subchronic MAP administration may produce an enduring change at the presynaptic cell membrane of the nerve terminal, which may in turn cause an increase in MAP uptake (by DA transporter) with a subsequent increase in DA release to the synaptic cleft. To confirm this hypothesis, we examined the changes in biodistribution of [^<125>I]RTI 55 (an analogue of cocaine) in the MAP-, and cocaine-sensitized rat brain. In MAP-sensitized rat, radioactivity of [^<125>I]RTI 55 increased significantly more in the frontal cortex, striatum, nucleus accumbens, thalamus, amygdala, hippocampus, ventral tegmental area, substantia nigra, cerebellum and pons. In cocaine-sensitized rat, radioactivity of [^<125>I]RTI 55 decreased significantly more in the same brain area. [^<123>I]IMP study showed these changes not due to alterations in metabolism or cerebral blood flow. Dopamine transporter has a structure similar to those of the other monoamine transporters. It seems possible that MAP and cocaine may bind to the 5-HT and noradrenaline transporters as well as DA transporter. Accordingly, it is concluded that subchronic administration of MAP or cocaine may cause a lasting change at the presynaptic cell membrane (including monoamine transporters) of the nerve terminal, though the direction of the changes of MAP- and cocaine-sensitized rats were controversial. This study comfirmed the hypothesis which lsubchronic MAP and cocain

  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Matsuoka,H.et al.: "Visual information processing deficits and vulnerability in Schizophrenia;biological and cognitive implications of the unomaly in NA potential." The Japanese Journal of Paychiatry and Neurology. 47. 694 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuoka,H.: "The seizure prognosis of juvenile myoclonic epilepsy." The Japanese Journal of Paychiatry and Neurology. 46. 293-296 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 松岡 洋夫: "精神分裂病の発症脆弱性-精神生理学アプローチ-" 脳と精神の医学. 3. 139-147 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Numachi,Y.et al.: "Alterations in biodistribution of ^<11>C-methamphetamine(MAP),^<14>C-MAP,and ^<123>I-N-isopsopyl-iodoamphetamine(IMP)in MAP-and cocaine-sensitized animals." Annals of The New York Academy of Sciences. 654. 153-159 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Numachi,Y.et al.: "Changes of drug biodistribution in the methamphetamine sensitized rat brain." Clinical Neuropharmacology. 15. 644A-645A (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 沼知 陽太郎,他: "メタンフェタミン逆耐性ラットにおける[^<125>I]RTI55の脳内分布の変化-オートラジオグラフィー法を用いた検討." 神経化学. 31. 272-273 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Numachi,Y.et al.: "Radioimage analysis of biodistribution of [^<125>I]RTI 55 in rat brain after subchronic central stimulants." Neurochemical Research. 18. 826 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Numachi,Y.et al.: "Radioimage analysis of biodistribution of [^<125>I]RTI 55 in rat brain after subchronic administration of cocaine." The Japanese Journal of Psychiatry and Neurology. 47. 703 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Numachi,Y.et al.: "Neural mechanism of stimulant-induced psychosis:secondary brain damage following methamphetamine dependence." The Japanese Journal of Pharmacology. 64. 61P (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉田 寿美子,他: "メタンフェタミン、コカイン反復投与による^3H-WIN35,428のラット脳内集積の変化." 神経化学. 31. 274-275 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐藤 光源,他: "てんかんと精神病との生物学的関連." 脳と精神の医学. 4. 83-85 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida,S.et al.: "Changes in biodistribution of a cocaine analogue,[^3H]WIN35,428,in rat brain after subchronic administration of central stimulants." Neurochemical Research. 18. 826 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐藤 光源: "精神疾患の再発をめぐって-その病態、機構、予防、シンポジウム総括." 脳と精神の医学. 3. 207-209 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato,M.et al.: "Relapse of paranoid psychotic state in methamphetamine model of Schizophrenia" Schizophrenia Bulletin. 18. 115-122 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato,M.: "A lasting vulnerability to psychosis in patients with provious MAP psychosis." Annals of The New York Academy of Sciences. 654. 160-170 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山本 芳正、他: "メタンフェタミン(MAP)逆耐性の形成に及ぼす拘束ストレスの影響." 薬物・精神・行動. 12. 300 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 松岡 洋夫(分担): "事象関連電位-事象関連電位と神経情報科学の発展" 新興医学出版社(in press), (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐藤 光源(分担): "精神分裂病の発症脆弱性:脳機能の解明-分子から病態まで" 創風社(in press), (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 沼知 陽太郎、他(分担): "神経伝達物質update-基礎から臨床まで(第2版)" 中外医学社, 10 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐藤 光源、他(分担): "精神分裂病はどこまでわかったか" 星和書店, 43 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐藤 光源(分担): "精神医学の進歩と動向" 文光堂, 11 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuoka, H., Sasaki, M., Sakashiata, T., Tashiro, S., Yamamoto, Y., Yoshida, S., Numachi, Y., Ueno, T., Saito, H., Fuse, Y., Matsue, Y.and Sato, M.: "Visual information processing deficits in Schizophrenia : biological and cognitive implications of the anomaly in NA potential" The Japanese Journal of Psychiatry and Neurology. Vol.47, No.3. 694 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuoka, H.: "The seizure prognosis of juvenile myoclonic epilepsy" The Japanese Journal of Psychiatry and Neurology. Vol.46, No.2. 293-296 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Numachi, Y., Yoshida, S., Inosaka, T., Sato, M., Mizugaki, M., Kimura, K.and Hishinuma, T.: "Alterations in biodistribution of ^<11>C-methamphetamine (MAP), ^<14>C-MAP, and ^<123>I-N-isopropyl-iodoamphetamine(IMP) in MAP- and cocaine-sensitized animals" Annals of The New York Academy of Sciences. Vol.654. 153-159 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Numachi, Y., Yoshida, S., Inosaka, T.and Sato, M.: "Changes of drug biodistribution in the methamphetamine sensitized rat brain" Clinical Neuropharmacology. Vol.15, Suppolement 1 Part A. 644A-645A (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Numachi, Y., Yoshida, S., Nakagawa, T., Matsuoka, H.and Sato, M.: "Radioimage analysis of [^<125>I]RTI 55 in rat brain after subchronic administration of cocaine" The Japanese Journal of Psychiatry and Neurology. Vol.47, No.3. 703 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Numachi, Y., Yoshida, S., Ito, T., Nakagawa, T., Matsuoka, H.and Sato, M.: "Radioimage analysis of biodistribution of [^<125>I]RTI 55 in rat brain after subchronic central stimulants" Neurochemical Research. Vol.18, No.7. 826 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida, S., Numachi, Y., Inosaka, T., Ito, T., Matsuoka, H.and Sato, M.: "Changes in biodistribution of a cocaine analogue, [^3H]WIN 35, 428, in rat brain after subchronic administration of central stimulants" Neurochemical Research. Vol.18, No.7. 826 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato, M., Numachi, Y.and Hamamura, T.: "Relapse of paranoid psychotic state in methamphetamine psychotic state in methamphetamine psychosis parallels" Schizophrenia Bulletin. Vol.18, No.1. 115-122 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato, M.: "A lasting vulnerability to psychosis in patients with previous methamphetamine psychosis" Annals of The New York Academy of Sciences. Vol.654. 160-170 (1992)

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

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Published: 1995-03-27  

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