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The mechanisms of anesthetic abuse

Research Project

Project/Area Number 13671622
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionKansai Medical University

Principal Investigator

NAKAO Shinichi  Kansai Medical University, Faculty of Medicine, Associate professor, 医学部, 助教授 (10207714)

Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsNucleus accumbens / Dopamine / Drug Abuse / Posterior cingulate and retrosplenial cortices / Ketamine / Nitrous Oxide / Xenon / Sigma 1 receptor / IP3受容体 / プロポフォール / プラジキニン / シグマ受容体 / ドロペリドール / デクスメデトミジン / 非競合性NMDA受容体拮抗薬
Research Abstract

I have investigated the effects of various anesthetics on dopamine release in the rat nucleus accumbens(Ncs), which is closely related to drug addiction and psychotomimetic activity of drugs, and c-Fos expression in the rat posterior cingulate and retrosplenial cortices(PC/RS), which are considered to represent psychotomimetic activity of NMDA receptor antagonists. I have also studied the effects of several intravenous anesthetics on sigma 1 receptors, which have various CNS effects including drug addiction.
Ketamine and nitrous oxide increased dopamine release in the Nac but xenon tended to decrease it. Repetitive administration of ketamine and nitrous oxide for 5 days did not further increase the dopamine release. Pentobarbital decreased the dopamine release and inhibited the ketamine-induced increase in dopamine release. Ketamine and nitrous oxide induced marked c-Fos expression in the PC/RS but xenon did not induce it. Nitrous oxide augmented the ketamine-induced c-Fos expression but xenon inhibited it. Clinically relevant doses of propofol affected sigma 1 receptor by a receptor binding assay, indicating that various CNS effects, such as drug addiction, psychotic activity, neuroprotection and anti-emetic activity, by propofol may be mediated, at least partly, by sigma 1 receptors.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Etsuko Miyamoto: "Caudoputamen is damaged by hypocapnia during mechanical ventilation in a rat model of chronic cerebral hypoperfusion"Stroke. 32. 2920-2925 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Atsushi Nagata: "Xenon Inhibits but N2O Enhances Ketamine-Induced c-Fos Expression in the Rat Posterior Cingulate and Retrosplenial Cortices"Anesthesia & Analgesia. 92. 362-368 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nobuyasu Nishizawa: "Inhibition of the N-methyl-D-aspartate receptor channel by local anesthetics in mouse CA1 pyramidal neurons"Anesthesia & Analgesia. 94. 325-330 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中尾 慎一: "薬物耽溺(Drug Abuse or Addiction)のメカニズム-麻酔関係薬物の耽溺を中心に"臨床麻酔(増刊号). 26. 413-425 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinichi Nakao: "Ketamine-induced c-Fos expression in the mouse posterior cingulate and retrosplenial cortices is mediated not only via NMDA receptors but also via sigma receptors"Brain Research. 926. 191-196 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 中尾 慎一: "N-methyl-D-aspartate (NMDA)受容体拮抗薬の神経細胞障害と精神異常誘発作用(ケタミンと亜酸化窒素を中心に)"麻酔. 52. 594-602 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinichi Nakao: "The inhibitory effect of propofol on ketamine-induced c-Fos expression in the rat posterior cingulate and retrosplenial cortices is mediated by GABAA receptor activation"Acta Anaesthesiol Scand. 47. 284-290 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Munehiro Masuzawa: "Pentobarbital inhibits ketamine-induced dopamine release in the rat nucleus accumbens : a microdialysis study"Anesthesia & Analgesia. 96. 148-152 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Etsuko Miyamoto: "Ketamine attenuates hypoxia-induced neuronal damage in the caudoputamen in a rat model of chronic cerebral hypoperfusion"Neuroscience Letters. 354. 26-29 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Etsuko Miyamoto: "Caudoputamen is damaged by hypocapnia during mechanical ventilation in a rat model of chronic cerebral hypoperfusion"Stroke. 32. 2920-2925 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Atsushi Nagata: "Xenon inhibits but N_2O enhances ketamine-induced c-Fos expression in the rat posterior cingulate and retrosplenial cortices"Anesth & Analg. 92. 326-368 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nobuyasu Nishizawa: "Inhibition of the N-methyl-D-aspartate receptor channel by local anesthetics in mouse CA1 pyramidal neurons"Anesth & Analg. 94. 325-330 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinichi Nakao: "The mechanisms of anesthetic drug abuse"Clinical Anesthesia(Japanese). 26. 413-425 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinichi Nakao: "Ketamine-induced c-Fos expression in the mouse posterior cingulate and retrosplenial cortices is mediated not only via NMDA receptors but also sigma receptors"Brain Research. 926. 191-196 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinichi Nakao: "Neuronal damage and psychotomimetic activity by NMDA receptor antagonists"Masui(Japanese). 52. 594-602 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinichi Nakao: "The inhibitory effect of propofol on ketamine-induced c-Fos expression in the posterior cingulate and retrosplenial cortices is mediated by GABAA receptor activation"Acta Anaesthesiol Scand. 47. 284-290 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Munehiro Masuzawa: "Pentobarbital inhibits ketamine-induce dopamine release in the rat nucleus accumbens : a microdialysis study"Anesth & Analg. 96. 148-152 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Etsuko Miyamoto: "Ketamine attenuates hypoxia-induced neuronal damage in the caudoputamen in a rat model of chronic cerebral hypoperfusion"Neurosci Lett. 354. 26-29 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinich Nakao: "The inhibitory effect of propofol on ketamine-induced c-Fos expression in the posterior cingulate and retrosplenial cortices is mediated by GABAA receptor activation"Acta Anaesthesiol Scand. 47. 284-290 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Uka Uchiyama: "Integrated pharmacological preconditioning in combination with adenosine, a mitochondrial KATP channel opener and a nitric oxide donor"J Thorac Cardiov Sur. 126. 148-159 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shinichi Nakao: "Is the attenuation of the extracellular dopamine increase in the nucleus accumbens the major mechanism by which dexmedetomidine increases the cocaine seizure threshold in rats?"Anesthesiology. 98. 1520-1520 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Uka Uchiyama: "Role of mitochondrial KATP channels and protein kinase C in ischaemic preconditioning"Chin Exp Pharmacol Physiol. 30. 426-436 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中尾慎一: "N-methyl-D-aspartate(NMDA)受容体拮抗薬の神経細胞傷害と精神異常誘発作用(ケタミンと亜酸化窒素を中心に)"麻酔. 52. 594-602 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Etsuko Miyamoto: "Ketamine attenuates hypoxia-induced neuronal damage in the caudoputamen in a rat model of chronic cerebral hypoperfusion"Neurosci Lett. 354. 26-29 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kouhei Murao: "Anticonvulsant effects of sevoflurane on amygdaloid kindling and bicuculline-induced seizures in rats : comparison with isoflurane and halothane"Journal of Anesthesia. 16. 34-43 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Munehiro Masuzawa: "Pentobarbital inhibits ketamine-induced dopamine release in the rat nucleus accumbens : a microdialysis study"Anesthesia Analgesia. 96. 148-152 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] "Ketamine prevents hypocapnia-induced neuronal damage in the caudoputamen in chronic cerebral hypoperfusion rats"Anesthesiology. A758. (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shinichi Nakao: "The inhibitory effect of propofol on ketamine-induced c-Fos expression in the posterior cingulate and retrosplenial cortices is mediated by GABAA receptor activation"Acta Anaesthesiologica Scandinavica. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 中尾慎一: "N-methyl-aspartate (NMDA)受容体拮抗薬の神経細胞傷害と精神異常誘発作用(ケタミンと亜酸化窒素を中心に)"麻酔. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takefumi Inada: "Propofol depressed neutrophil hydrogen peroxide production more than midazolam, whereas adhesion molecule expression was minimally affected by both anesthetics in rats with abdominal sepsis"Anesthesia & Analqesia. 92. 437-441 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Atsushi Nagata: "Xenon inhibits but N20 enhances ketamine-induced c-Fos expression in the rat posterior cingulate and retrosplenial cortices"Anesthesia & Analgesia. 92. 362-368 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Etusko Miyamoto: "Caudoputamen is damaged by hypocapnia during mechanical ventilation in a rat model of chronic cerebral hypoperfusion"Stroke. 32. 2920-2925 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nobuyasu Nishizawa: "Inhibition of the N-methyl-D-aspartate receptor channel by local anesthetics in mouse CA1 pyramidal neurons"Anesthesia & Analgesia. 94. 325-330 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinichi Nakao: "Ketamine-induced c-Fos expression in the mouse posterior cingulate and retrosplenial cortices is mediated not only via NMDA receptors but also sigma receptors"Brain Research. 926. 191-196 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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