Effects of selective inhibitors of GABAA alpha5 subunit on postoperative cognitive function and pain

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K18272
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Osaka University
• Principal Investigator: Iura Akira 大阪大学, 大学院医学系研究科, 助教 (40467551)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: GABAA受容体 / α5サブユニット / Tonic電流

Outline of Final Research Achievements

In this study, we investigated effects of selective inhibitors of GABAA receptor α5 subunit on postoperative cognitive function and pain. Buprenorphine was administered to a mouse model of postoperative pain for analgesia, and the mice were randomly divided into two groups: group L, which received L-655708, a GABAA receptor α5 subunit inhibitor, and group N, which received saline as a control. Results of behavioral experiments confirmed that L-655708 could be safely administered. Spinal cord slices were prepared from mice, and whole-cell patch clamps were performed on spinal cord dorsal horn SG cells while perfused with artificial cerebrospinal fluid to record cell currents. After potential fixation at 0 mV and baseline recording, L-655708 was added to the perfusion solution and GABAA receptor α5 subunit-mediated current was measured.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

全身麻酔後の認知機能障害の予防策ないし治療法を開発することは、非常に重要な意義を持つと考えられる。記憶・学習を司る海馬に多く存在することが知られているGABAA受容体α5サブユニットに対する選択的阻害薬の投与により、海馬の神経細胞の興奮性を増強することで、記憶・学習の効率を高めることができるのではないかと期待されている。
本研究では、マウスの全身麻酔術後疼痛モデルに対してGABAA受容体α5サブユニット選択的阻害薬を投与し、記憶・学習機能に対する効果を調べた。また、術後疼痛に与える影響を行動学実験及び脊髄スライスを用いたパッチクランプによる電気生理学実験で検証した。