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1999 Fiscal Year Final Research Report Summary

Analysis for the physiological role of a novel GABAィイD2AィエD2 receptor sub-class.

Research Project

Project/Area Number 10670149
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionTOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH (1999)
Tokyo Metropolitan Institute for Neuroscience (1998)

Principal Investigator

ONOE Hirotaka  Tokyo Metropolitan Institute for Neuroscience, Dept. Psychology, 東京都神経科学総合研究所, 主任研究員 (80214196)

Co-Investigator(Kenkyū-buntansha) WATANABE Yashuyoshi  Osaka Bioscience Institute, Dept. Neuroscience, 第3部門, 研究部長 (40144399)
Project Period (FY) 1998 – 1999
Keywordspositron emission tomography / GABAィイD2AィエD2 receptor / Benzodiazepine / monkey / Ro15-4513 / limbic system / anterior cingulate
Research Abstract

Previously, we revealed the presence of very high- and high-affinity binding sites (ex. Kd values in the amygdala are ca. 0.4 and 18.7 nM, respectively) in the γ-aminobutyric acid/benzodiazepine (GABAィイD2AィエD2/BZ) receptor in the living monkey brain by an in vivo saturation study using ィイD111ィエD1C-labeled Ro15-4513 with high specific radioactivity (>70 GBq/μmol). To assess the physiological function of the very high-affinity binding sites of GABAィイD2AィエD2/Benzodiazepine (BZ) receptor in the intact living brain, the binding of a ィイD111ィエD1C-labeled BZ partial inverse agonist ([ィイD111ィエD1C]Ro15-4513) of the GABAィイD2AィエD2/BZ receptor was investigated by the positron emission tomography (PET) with conscious and anesthetized monkeys. In the conscious monkey, sleep deprivation or ketamine, a NMDA receptor blocker, treatment increased the binding of [ィイD111ィエD1C]Ro15-4513, but not did that of [ィイD111ィエD1C]Ro15-1788. Furthermore, propofol, a positive allosteric modulator of the GABAィイD2AィエD2/BZ receptors, anesthesia induced decreases in the binding of [ィイD111ィエD1C]Ro15-4513 but not did that of [ィイD111ィエD1C]Ro15-1788. The very high affinity binding sites of [ィイD111ィエD1C]Ro15-4513 were invisible in the most of limbic regions under the propofol anesthesia. These results strongly indicate that the binding characteristics of the [ィイD111ィエD1C]Ro15-4513 in vivo may be related to both the heterogeneity of GABAィイD2AィエD2/BZ receptor and its efficacy modulated by allosteric agents in the living brain.

  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] 尾上浩隆: "サル脳の非侵襲機能マッピング"脳21. 2・2. 197-201 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 尾上浩隆、渡辺恭良: "陽電子断層撮像法(PET)によるサル脳のイメージング"脳の科学. 21・8. 862-866 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 尾上浩隆: "陽電子断層撮像法(PET)を用いた睡眠研究"脳床脳波. 42・2. 69-73 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Onoe, H.: "Non-invasive bran mapping for the monkey brain."Brain 21. 2(2). 197-201 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Onoe, H., Watanabe. Y.: "Brian imaging for monkey by positron emissiotomography (PET)."Brain Science. 21(8). 862-866 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Onoe, H.: "Positron emission tomography (PET) as a research tool in the investigation of sleep."Clinical Electroence-phalography. 42(2). 69-73 (2000)

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

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Published: 2001-10-23  

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