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Brain orexinergic-noradrenergic neurons and mechanism of general anesthesia

Research Project

Project/Area Number 17390423
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

HIROTA Kazuyoshi  Hirosaki University, Hirosaki University, Graduate School of Medicine, Professor (20238413)

Co-Investigator(Kenkyū-buntansha) KUDO Mihoko  Hirosaki University, Graduate School of Medicine, Assistant Professor (30003411)
KUSHIKATA Tetsuya  Hirosaki University, University Hospital, Lecturer (80250603)
KUDO Tsuyoshi  Hirosaki University, Graduate School of Medicine, Assistant Professor (70003407)
YOSHIDA Hitoshi  Hirosaki University, University Hospital, Assistant Professor (00374843)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥10,440,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥840,000)
Fiscal Year 2007: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2006: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordsorexin / noradrenaline / rat / microdialysis / cerebrocortical slice / ノルエピネフリン / 大脳皮質 / 電撃痙攣療法 / α受容体作リガンド / ベンゾジアゼピン / 神経組織 / 吸入麻酔薬 / 静脈麻酔薬
Research Abstract

The present data support our hypothesis that both inhibition and overexcitation of noradrenergic neurons by GABA-type and NMDA-type of anesthetics, respectively, contribute to the mechanism of general anesthesia (=loss of consciousness). Orexin increases noradrenergic neuronal activity but the increase is saturable around 250% of the basal, whose level of noradrenergic neuronal activity may induce the maximal wakefulness in our hypothesis. In addition, the present data indicates that orexinergic neurons could be a target for both GABA-type and NMDA-type of anesthetic agents as orexin decreased both barbiturates (GABA-type) and ketamine (NMDA-type)-produced anesthesia time. Orexin also antagonized thiopental-induced inhibition of and ketamine-caused overexcitatio of noradrenergic activity. Yohimbin 10 mg/kg ip increased cerebral noradrenaline release to ~500% of the basal, and this increase prolonged GABA-type anesthetic propofol-produced anesthesia time. This means that overexcitation of noradrenergic neuronal activity could also enhance GABA-type anesthetics-produced anesthesia. It is known that DSP-4 lesions locus coeruleus-originated noradrenergic neurons. The lesion increased thiopental anesthesia time and decreased ketamine anesthesia time. In addition, there were significant correlations between cerebral noradrenaline contents and increase in thiopental anesthesia time or decrease in ketamine anesthesia time. Therefore, we proved our hypothesis that both inhibition and overexcitation of noradrenergic neurons contribute to loss of consciousness.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (30 results)

All 2008 2007 2006 2005

All Journal Article (17 results) (of which Peer Reviewed: 7 results) Presentation (13 results)

  • [Journal Article] Role of the orexinergic system in acute haemorrhage in the rat.2008

    • Author(s)
      Hirota K, Kushikata T, Yoshida H, Kudo M, Kudo T.
    • Journal Title

      Neurosci Lett 432

      Pages: 162-166

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] ノルアドレナリン神経ネットワークと全身麻酔機序.2008

    • Author(s)
      廣田和美、櫛方哲也.
    • Journal Title

      医学の歩み (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Role of the orexinergic system in acute haemorrhage in the rat2008

    • Author(s)
      Hirota K, Kushikata T, Yoshida H, Kudo M, Kudo T.
    • Journal Title

      Neurosci Lett 432

      Pages: 162-166

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Noradrenergic neuronal network and mechanism of general anesthesia2008

    • Author(s)
      Hirota K, Kushikata T.
    • Journal Title

      Igaku No Ayumi (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The effects of benzodiazepines on orexinergic systems in rat cerebrocortical slices.2007

    • Author(s)
      He Y, Kudo M, Kudo T, Kushikata T, Li E, Hirota K.
    • Journal Title

      Anesth Analg 104

      Pages: 338-340

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary 2006 Annual Research Report
    • Peer Reviewed
  • [Journal Article] オレキシンとノルエピネフリン覚醒システム.2007

    • Author(s)
      廣田和美.
    • Journal Title

      麻酔 56

      Pages: 9-18

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The effects of benzodiazepines on orexinergic systems in rat cerebrocortical slices2007

    • Author(s)
      He Y, Kudo M, Kudo T, Kushikata T, Li E, Hirota K.
    • Journal Title

      Anesth Analg 104

      Pages: 338-340

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Orexinergic neurons and noradrenergic awakening system in general anesthesia2007

    • Author(s)
      Hirota K.
    • Journal Title

      Masui 56

      Pages: 9-18

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] オレキシンとノルエピネフリン覚醒システム.2007

    • Author(s)
      廣田和美
    • Journal Title

      麻酔 56

      Pages: 9-18

    • Related Report
      2007 Annual Research Report 2006 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Special cases: ketamine, nitrous oxide and xenon.2006

    • Author(s)
      Hirota K.
    • Journal Title

      Best Pract Res Clin Anaesthesiol 202

      Pages: 69-79

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Special cases: ketamine, nitrous oxide and xenon2006

    • Author(s)
      Hirota K.
    • Journal Title

      Best Pract Res Clin Anaesthesiol 202

      Pages: 69-79

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Special cases : ketamine, nitrous oxide and xenon.2006

    • Author(s)
      Hirota K, Kudo M, Tose R, et al.
    • Journal Title

      Best Pract Res Clin Anaesthesiol 20

      Pages: 69-79

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Isoflurane increases norepinephrine release in the rat preoptic area and the posterior hypothalamus in vivo and in vitro: Relevance to thermoregulation during anesthesia.2005

    • Author(s)
      Kushikata T, Hirota K, Kotani N, Yoshida H, Kudo M, Matsuki A.
    • Journal Title

      Neuroscience 131

      Pages: 79-86

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Lack of interaction between orexinergic and alpha2-adrenergic neuronal systems in rat cerebrocortical slices.2005

    • Author(s)
      Hirota K, Kudo M, Tose R, Yoshida H, Kudo T, Kushikata T.
    • Journal Title

      Neurosci Lett 387

      Pages: 49-52

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Isoflurane increases norepinephrine release in the rat preoptic area and the posterior hypothalamus in vivo and in vitro: Relevance to thermoregulation during anesthesia2005

    • Author(s)
      Kushikata T, Hirota K, Kotani N, Yoshida H, Kudo M, Matsuki A.
    • Journal Title

      Neuroscience 131

      Pages: 79-86

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Lack of interaction between orexinergic and alpha2-adrenergic neuronal systems in rat cerebrocortical slices2005

    • Author(s)
      Hirota K, Kudo M, Tose R, Yoshida H, Kudo T, Kushikata T.
    • Journal Title

      Neurosci Lett 387

      Pages: 49-52

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Lack of interaction between orexinergic and α_2-adrenergic neuronal systems in rat cerebrocortical slices.2005

    • Author(s)
      Hirota K, Kudo M, Tose R, et al.
    • Journal Title

      Neuroscience Letters 387

      Pages: 49-52

    • Related Report
      2005 Annual Research Report
  • [Presentation] 内因性睡眠関連物質から見た麻酔機序-細胞から個体まで-.2007

    • Author(s)
      櫛方哲也
    • Organizer
      第54回日本麻酔科学会総会
    • Place of Presentation
      札幌市
    • Year and Date
      2007-05-31
    • Related Report
      2007 Annual Research Report
  • [Presentation] 亜酸化窒素の大脳皮質ノルアドレナリン放出に与える影響.2006

    • Author(s)
      吉田仁、櫛方哲也、遠瀬龍二、工藤美穂子、石原弘規、廣田和美
    • Organizer
      第53回日本麻酔科学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2006-06-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] オレキシンがケタミンン麻酔に与える影響-ノルアドレナリン作動性神経活性との関連において-.2006

    • Author(s)
      遠瀬龍二、櫛方哲也、吉田仁、安田忠伸、工藤美穂子、工藤剛、廣田和美
    • Organizer
      第53回日本麻酔科学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2006-06-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 出血性ショックは血漿中のオレキシンA(OXA)濃度を増加させる.-オレキシン受容体拮抗薬SB-334867を用いた研究-.2006

    • Author(s)
      櫛方哲也、廣田和美、吉田仁、遠瀬龍二、工藤美穂子
    • Organizer
      第53回日本麻酔科学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2006-06-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Effects of nitrous oxide on noradrenaline release from the cerebral cortex in rats2006

    • Author(s)
      Yoshida H, Kushikata T, Tose R, Kudo M, Ishihara H, Hirota K.
    • Organizer
      The 53th Annual Meeting of Japan Society of Anesthesiolohists
    • Place of Presentation
      Kobe
    • Year and Date
      2006-06-01
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Effects of orexin on ketamine anesthesia. The relation with activity of noradrenergic neurons2006

    • Author(s)
      Tose R, Kushikata T, Yoshida H, Yasuda T, Kudo M, Kudo T, Hirota K.
    • Organizer
      The 53th Annual Meeting of Japan Society of Anesthesiolohists
    • Place of Presentation
      Kobe
    • Year and Date
      2006-06-01
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Plasma orexin A increases by hemorrhagic shock2006

    • Author(s)
      Kushikata T, Hirota K, Yoshida H, Tose R, Kudo M.
    • Organizer
      The 53th Annual Meeting of Japan Society of. Anesthesiolohists
    • Place of Presentation
      Kobe
    • Year and Date
      2006-06-01
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Orexin decreased ketamine anesthesia time in rat. -Relevance to brain noradrenergic neuronal activity2006

    • Author(s)
      Tose R, Kushikata T, Yoshida H, Yasuda, Kudo M, Hirota K.
    • Organizer
      80th Clinical and Scientific Congress of International A nesthesia Research Society,
    • Place of Presentation
      San Francisco
    • Year and Date
      2006-03-26
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Orexin decreased ketamine anesthesia time in rat. -Relevance to brain noradrenergic neuronal activity2006

    • Author(s)
      Tose R, Kushikata T, Yoshida H, Yasuda, Kudo M, Hirota K.
    • Organizer
      80th Clinical and Scientific Congress of International Anesthesia Research Society
    • Place of Presentation
      San Francisco
    • Year and Date
      2006-03-26
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] オレキシンによるラット大脳皮質スライスからの選択的ノルエピネフリン放出に対するベンゾジアゼピンの抑制効果.2005

    • Author(s)
      櫛方哲也、工藤美穂子、工藤剛、廣田和美
    • Organizer
      第12回日本静脈麻酔・Infusion Technology研究会
    • Place of Presentation
      千葉
    • Year and Date
      2005-12-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The effects of benzodiazepines on orexinergic systems in rat cerebrocortical slices2005

    • Author(s)
      Kushikata T, Kudo M, Kudo T, Hirota K.
    • Organizer
      The 12^<th> Japan Society for Intravenous Anesthesia And Infusion Technology
    • Place of Presentation
      Chiba
    • Year and Date
      2005-12-10
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] オレキシン作動性神経とアルファ2受容体の相互作用の欠如について.2005

    • Author(s)
      櫛方哲也、遠瀬龍二、吉田仁、廣田和美.
    • Organizer
      第52回日本麻酔科学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2005-06-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Lack of interaction between orexinergic and alpha2-adrenergic neuronal systems in rat cerebrocortical slices2005

    • Author(s)
      Kushikata T, Tose R, Yoshida H, Hirota K.
    • Organizer
      The 52th Annual Meeting of Japan Society of Anesthesiolohists
    • Place of Presentation
      Kobe
    • Year and Date
      2005-06-01
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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