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Effects of general anaesthetics and sedatives on central dopaminergic neuronal activity : a microdialysis study

Research Project

Project/Area Number 04671138
Research Category

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

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionNihon University

Principal Investigator

KOSHIKAWA Noriaki  Nihon University, School of Dentistry, Associate Professor, 歯学部, 助教授 (80130491)

Co-Investigator(Kenkyū-buntansha) TAKADA Koji  Nihon University, School of Dentistry, Lecturer, 歯学部, 講師 (00216657)
KANAYAMA Toshiyoshi  Nihon University, School of Dentistry, Professor, 歯学部, 教授 (40224589)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
KeywordsStriatum / Nucleus accumbens / Dopamine release / Benzodiazepine receptor / Adenosine receptor / alpha_2-Adrenoceptor / Opioid receptor / Microdialysis / オピエ-ト受容体 / フェンタニール / ミダゾラム / ドパミン / 中脳腹側被蓋野 / フルマゼニール / beta-CCE / アデノシン性神経 / フルニトラゼパム
Research Abstract

Effects of benzodiazepine anaesthetics or sedatives on central dopaminergic neuronal activity were studied by using in vivo brain microdialysis to measure dopamine release from the striatum and the nucleus accumbens. Effects of the drugs often coadministered in clinic with the anaesthetics, i.e.clonidine and fentanyl, on central dopaminergic neuronal activity were also studied. Intravenous injections of midazolam and flunitrazepam decreased striatal dopamine release in a dose-dependent manner. Flumazenil also did not affect striatal dopamine release, but it prevented the effects of midazolam and flunitrazepam. Flunitrazepam also decreased striatal dopamine release when infused into the striatum, but it failed to affect the dopamine release when infused into the ipsilateral substantia nigra. Central administrations of midazolam were effective only when the drug was infused into both sites simultaneously. Intravenous injections of midazolam also dose-dependently decreased dopamine release from the nucleus accumbens. In contrast, the benzodiazepine receptor inverse agonist, beta-CCE,dosedependently increased the dopamini release. The effects of both drugs were prevented again by flumazenil. Moreover, adenosine receptors were not suggested to be involved in the benzodiazepine receptor-mediated dopamine decrease from the nucleus accumbens. Clonidine, an alpha_2-adrenoceptor agonist, decreased dopamine release from the nucleus accumbens, and enhanced the effects of midazolam. The results are suggestive of clinical use of clonidine to reduce the anaesthtic requirement of midazolam when used as a premedicant. Fentanyl, an opioid analgesic, increased dopamine release from the nucleus accumbens in a does-dependent manner. The effects were suggested to be mediated by the nucleus accumbens mechanisms. Furthermore, the effects of fentanyl was inhibited by midazolam infused into the nucleus accumbens but not infused into the ventral tegmental area.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Koji,Takada: "Effects of midazolam and flunitrazepan on the release of dopamine from rat striatum measured by in vivo microdialysis" British Journal of Anaesthesia. 73. 181-185 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tameatsu Murai: "Opposite effects of midazolam and β-carboline-3-carboxylate ethyl ester on the release of dopamine from rat nucleus accumbens measured by in vivo microdialysis" European Journal of Pharmacology. 261. 65-71 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takada, K., Murai, T., Kanayama, T.and Koshikawa, N: "Effects of midazolam and flunitrazepam on the release of dopamine from rat striatum measured by in vivo microdialysis" British Journal of Anaesthesia. 70. 181-185 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Murai, T., Koshikawa, N., Kanayama, T.Takada, K.and Kobayashi, M: "Opposite effects of midazolam and -carboline-3-carboxylate ethyl ester on the release of dopamine from rat nucleus accumbens measured by in vivo microdialysis" European Journal of Pharmacology. 261. 65-71 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tameatsu Murai: "Opposite effects of midazolam and β-carbcline-3-carbcxylate ethyl ester on the release of dcpamine from rat nucleus accumbens measured by in vivo microdialysis" European Journal of Pharmacology. 261. 65-71 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 富山勝則: "α_2-Adrenoceptorによる側坐核 dopamine遊離調節機構;GABAA/benzodiazepine receptor関与の可能性" 神経化学. 33. 38-39 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 富山勝則,村井〓敦,越川憲明,小〓雅文: "側坐核Dopaminre遊離に及ぼすBenzodiazepine受容体AgonistおよびIwverse-agonistの効果" 神経化学. 32. 218-219 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 村井〓敦,越川憲明,京田直人,貝崎徹,金山利吉: "ミダゾウムおよびbeta-CCEがウット側坐核ドーパミン遊離に及ぼす効果" PHARMACOANESTHESIOLOGY. 6(2). 37-38 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] K.TAKADA , T . MURAI, T.KANAYAMA and N.KOSHIKAWA: "Effects of midazolam and flunitrazepam on the release of dopamine from rot striatum measured by INVIVO microdialysis" British Journal of Anaesthesia. 70. (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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