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The role of GABAAreceptors and inhibitory neuron network on anesthetic-induced neural inhibition

Research Project

Project/Area Number 17390425
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

NISHIKAWA Koichi  Gunma University, Graduate School of Medicine, Associate professor (00334110)

Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥12,250,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥8,800,000 (Direct Cost: ¥8,800,000)
KeywordsSynaptic transmission / GABA receptor / Plasticity / Anesthetics / Amnesia / Hypnosis / Patch clamp / Memory / 抑制ニューロン / GABA合成酵素ノックアウト動物 / 海馬スライス標本 / シナプス電流 / 立ち直り反射 / GABA / 吸入麻酔薬 / シナプス可塑性 / 神経因性疼痛 / GABA合成酵素ノックアウトマウス
Research Abstract

Background: The cellular mechanisms of anesthetic-induced amnesia are still poorly understood. The present study examined the effects of sevoflurane at various concentrations on excitatory synaptic transmission and on long-term potentiation (LTP) as a possible mechanism contributing to loss of recall in the CA1 region of rat hippocampal slices. Methods: Population spikes (PS) and field excitatory postsynaptic potentials (fEPSPs) were recorded using extracellular electrodes following electrical stimulation of Schaffer-collateral-commissural (SCC) fiber inputs. Paired pulse facilitation (PPF) was used as a measure of presynaptic effects of the anesthetic LTP was induced using tetanic stimulation (100 Hz, 1 s) of the SCC pathway. Sevoflurane at subanesthetic (0.5%) to anesthetic concentrations (28-5.0%) was applied to slices in artificial cerebrospinal fluid solution.
Results: In the presence of subanesthetic sevoflurane (0.5%), PS amplitude was significantly depressed and tetanic stimulation induced only post-tetanic potentiation (PTP) and then failure of LTP. These inhibitory effects were antagonized by bicuculline (10μM), a GABA_A receptor antagonist. In addition, anesthetic sevoflurane further depressed fEPSP amplitude in a dose-dependent manner, and completely blocked LTP. Bicuculline only partially antagonized anesthetic sevoflurane-induced profound inhibition of LTP. Anesthetic but not subanesthetic, sevoflurane significantly increased PPF, suggesting that anesthetic sevoflurane has presynaptic actions to reduce glutamate release from nerve terminals.
Conclusions: The present study provides evidence that subanesthetic sevoflurane inhibits long-term potentiation of hippocampal CA1 neurons through GABAergic mechanisms, and these actions alone seem to account for the effects of subanesthetic sevoflurane on synaptic plasticity.

Report

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

    (24 results)

All 2008 2007 2006 2005

All Journal Article (19 results) (of which Peer Reviewed: 6 results) Presentation (3 results) Book (2 results)

  • [Journal Article] Amnestic concentrations of sevoflurane inhibit synaptic plasticity of hippocampal CA1 neurons through GABAergic mechanisms.2008

    • Author(s)
      Ishizeki J, Nishikawa K, Kubo K Saito S, Goto F
    • Journal Title

      Anesthesiology 108

      Pages: 447-56

    • 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] Amnestic concentrations of sevoflurane inhibit synaptic plasticity of hippocampal CAl neurons through GABAergic mechanisms2008

    • Author(s)
      Ishizeki J, Nishikawa K, Kubo K, Saito S, Goto F
    • Journal Title

      Anesthesiology 108

      Pages: 447-56

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Amnestic concentrations of sevoflurane inhibit synaptic plasticity of hippocampal CAIneurons through GABAergic mechanisms.2008

    • Author(s)
      Ishizeki I, Nishikawa K, Kubo K Saito S, Goto F
    • Journal Title

      Anesthesiology 108

      Pages: 447-56

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of effects of rapid colloid loading before and after spinal anesthesia on maternal hemodynamics and neonatal outcomes in cesarean section.2007

    • Author(s)
      Nishikawa K, Yokoyama N, Saito S, Goto F
    • Journal Title

      Journal of Clinical Monitoring and Computing 21

      Pages: 125-129

    • 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 the extent of spinal block on the BIS score and regional cerebral oxygen saturation in elderly patients:-A prospective, randomized, and double-blinded study-2007

    • Author(s)
      Nishikawa K, Hagiwara R, Nakamura K, Ishizeki J, Kubo K, Saito S, Goto F
    • Journal Title

      Journal of Clinical Monitoring and Computing 21

      Pages: 109-114

    • 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 the extent of spinal block on the BIS score and regional cerebral oxygen saturation in elderly patients: -A prospective, randomized, and double-blinded study-2007

    • Author(s)
      Nishikawa K, Hagiwara R, Nakamura K, Ishizeki J, Kubo K, Saito S, Goto F
    • Journal Title

      Journal of Clinical Monitoring and Computing 21

      Pages: 109-114

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Comparison of effects of rapid colloid loading before and after spinal anesthesia on maternal hemodynamics and neonatal outcomes in cesarean section2007

    • Author(s)
      Nishikawa K, Yokoyama N, Saito S, Goto F
    • Journal Title

      Journal of Clinical Monitoring and Computing 21

      Pages: 125-129

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Comparigon of effects of rapid colloid loading before and after spinal anesthesia on matemal hemodynamics and neonatal outcomes in cesarean section.2007

    • Author(s)
      Nishikawa K, Yokoyama N. Saito S, Goto F
    • Journal Title

      Joumal of Clinical Monitoring and Computing 21

      Pages: 125-129

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The effectS of the extent of spinal block on theBIS score and regional cerebral oxygensaturation in elderly patientS:-A prospective,randomized,and double-blinded study-2007

    • Author(s)
      NiShikawa K, Hagiwara R, Nakamura K, Ishizeki J, Kubo K, Saito S, Goto F
    • Journal Title

      Joumal of Clinical Monitoring and Computing 21

      Pages: 109-114

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The effects of the extent of spinal block on the BIS score and regional cerebral oxygen saturation in elderly patients : -A prospective, randomized, and double-blinded study-2007

    • Author(s)
      Nishikawa K et al.
    • Journal Title

      Journal of Clinical Monitoring and Computing (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Comparison of effects of rapid colloid loading before and after spinal anesthesia on maternal hemodynamics and neonatal outcomes in cesarean section.2007

    • Author(s)
      Nishikawa K et al.
    • Journal Title

      Journal of Clinical Monitoring and Computing (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Bispectral index and regional cerebral oxygen saturation during propofol/N_2O anesthesia.2006

    • Author(s)
      Kanemaru Y, Nishikawa K, Goto F
    • Journal Title

      Canadian J Anesthesia 53

      Pages: 363-9

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The effects of volatile anesthetics on intraoperative monitoring of myogenic motor evoked potentials to trans cranial electrical stimulation and on partial heuromuscular blockade during propofol/fentanyl/nitrous oxide anesthesia in humans.2006

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

      Journal of Neurosurgical Anesthesiology 18

      Pages: 106-11

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The influence of sevoflurane on the bispectral index, regional cerebral oxygen saturation, and propofol concentration during propofol/N_2O anesthesia.2006

    • Author(s)
      Nishikawa K et al.
    • Journal Title

      Journal of Clinical Monitoring and Computing 20

      Pages: 415-20

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The interaction of noradrenaline with sevoflurane on GABAA receptor-mediated inhibitory postsvnaptic currents in the rat hippocampus.2005

    • Author(s)
      Nishikawa K, Kubo K, Ishizeki J, Takazawa T, Saito S, Goto F
    • Journal Title

      Brain Research 1039

      Pages: 153-161

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The monoamine-mediated antiallodynic effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a rat model of neuropathic pain.2005

    • Author(s)
      Obata H, Saito S, Koizuka S, Nishikawa K, Goto F
    • Journal Title

      Anesthesia and Analgesia 100

      Pages: 1406-1410

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A dopamine infusion decreases propofol concentration during epidural blockade under general anesthesia.2005

    • Author(s)
      Takizawa D, Nishikawa K, Sato E, Hiraoka H, Yamamoto K, Saito S, Horiuchi R, Goto F
    • Journal Title

      Canadian journal of Anesthesia 52

      Pages: 463-466

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Landiolol and esmolol prevent tachycardia without altering cerebral blood flow.2005

    • Author(s)
      Saito S, Nishihara F, Akihoro T, Nishikawa K, Obata H, Goto F, Yuki N
    • Journal Title

      Canadian journal of Anesthesia 52

      Pages: 1027-1034

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Femoral necrosis due to occlusion of the left common iliac artery in a patient with thromboangiitis obliterans.2005

    • Author(s)
      Nishikawa K, Goto F
    • Journal Title

      The Pain Clinic 17

      Pages: 209-212

    • Related Report
      2005 Annual Research Report
  • [Presentation] Altered responses to propofol,but not ketamine,in mice Iacking glutamic acid decarboxylase65.2007

    • Author(s)
      Nishikawa K, Kubo K, Yamada M, lshizeki J, Saito S, Goto F
    • Organizer
      American Society of Anesthesiologists meeting 2008
    • Place of Presentation
      San Francisco,USA
    • Year and Date
      2007-10-15
    • Related Report
      2007 Annual Research Report
  • [Presentation] Altered responses to propofol, but not ketamine, in mice lacking glutamic acid decarboxylase 65.2007

    • Author(s)
      Nishikawa K, Kubo K, Yamada M, Ishizeki J, Saito S, Goto F
    • Organizer
      American Society of Anesthesiologists meeting 2008
    • Place of Presentation
      San Francisco, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Altered responses to propofol, but not ketamine, in mice lacking glutamic acid decarboxylase 652007

    • Author(s)
      Nishikawa K, Kubo K, Yamada M, Ishizeki J, Saito S, Goto F
    • Organizer
      American Society of Anesthesiologists meeting at San Francisco
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 全身麻酔薬の中枢神経作用、麻酔科レビュー2006 (天羽敬祐 監修)2006

    • Author(s)
      西川 光一
    • Publisher
      総合医学社
    • Related Report
      2006 Annual Research Report
  • [Book] 全身麻酔薬の中枢神経作用 麻酔科レビュー2006-最新主要文献集-(天羽敬祐編)2006

    • Author(s)
      西川 光一
    • Total Pages
      5
    • Publisher
      総合医学社
    • Related Report
      2005 Annual Research Report

URL: 

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

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