The Role of GABA and Glutamate Neurons in General Anesthetic Action
| Project/Area Number |
13672097
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
KAWAHARA Michio (2002) Hiroshima University, Graduate School of Biomedical Sciences Professor, 大学院・医歯薬学総合研究科, 教授 (30034094)
入船 正浩 (2001) 広島大学, 歯学部, 助教授 (10176521)
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| Co-Investigator(Kenkyū-buntansha) |
DOHI Toshihiro Hiroshima University, Graduate School of Biomedical Sciences Professor, 大学院・医歯薬学総合研究科, 教授 (00034182)
河原 道夫 広島大学, 歯学部, 教授 (30034094)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | General anesthesia / Behavioral pharmacology / microdialysis / GABA / Glutamate / Gabaculine / NO-711 / Ketamine / GABAculine / 全身麻酔作用 / 正向反射 / GABA神経 / 脳内GABA濃度 / 内因性GABA |
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| Research Abstract |
General anesthetic state appears to include several components ; e.g., unconsciousness, amnesia, immobility and suppression of reflex responses. The state can be achieved by enhancing inhibitory neurotransmission (e.g., GABA neurons), by inhibiting excitatory neurotransmission (e.g., glutamate neurons) or by a combination of both. In this study, the effects of increased brain concentration of GABA were examined on anesthesia in mice. To increase the GABA concentration of the brain, the GABA-transaminase inhibitor gabaculine and the GABA uptake inhibitor NO-711 were administered intraperitoneally. General anesthetic action was evaluated using two procedures as the different end point ; a loss of the righting reflex (LORR) and a loss of the tail-pinch response. The LORR may reflect unconsciousness, and the loss of the tail-pinch response may reflect the integrated components of anesthesia. Gabaculine dose-dependently induced LORR with an ED_<50> value of 100 (75-134) mg/kg, but the highest dose (400 mg/kg) used in this study did not produce any loss of the tail-pinch response. In a brain microdialysis study, gabaculine (100 mg/kg) significantly increased extracellular GABA level (up to 3179.0% ^^+__- 314.9%) in the hippocampus. A high dose of NO-711 (50 mg/kg) induced ataxia, but produced neither the LORR nor the loss of the tail-pinch response. Increase in extracellular GABA level induced by NO-711 (50 mg/kg) was only 269.7% ^^+__- 24.2%. In contrast, the intravenous anesthetic propofol clinically used induced both the loss of the righting reflex and the tail-pinch response. In a previous study, we reported that propofol-induced anesthesia is mediated, at least in part, by both GABA and glutamate neurons. These findings suggest that general anesthetic action may be induced by the combination of enhancing inhibitory neurotransmission and inhibiting excitatory neurotransmission.
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Report
(3 results)
Research Products
(3 results)
