权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The Role of GABA and Glutamate Neurons in General Anesthetic Action

GABA 和谷氨酸神经元在全身麻醉作用中的作用

基本信息

批准号：
13672097
负责人：
KAWAHARA Michio
金额：
$ 2.62万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

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.

全身麻醉状态似乎包括几个组成部分;例如，无意识、健忘、不动和反射反应抑制。该状态可以通过增强抑制性神经传递（例如，GABA神经元），通过抑制兴奋性神经传递（例如，谷氨酸神经元）或两者的组合。在这项研究中，GABA的脑浓度增加的影响，在小鼠麻醉检查。为了增加脑的GABA浓度，将GABA-转氨酶抑制剂gabaculine和GABA摄取抑制剂NO-711腹膜内给药。使用两种程序作为不同的终点来评价全身麻醉作用;翻正反射（LORR）的丧失和夹尾反应的丧失。LORR可能反映无意识，夹尾反应的丧失可能反映麻醉的综合成分。加巴库林剂量依赖性地诱导LORR，艾德_<50>值为100（75-134）mg/kg，但本研究中使用的最高剂量（400 mg/kg）并未导致捏尾反应的任何损失。在脑微透析研究中，加巴库林（100 mg/kg）显著增加海马细胞外GABA水平（达3179.0% ^^+__- 314.9%）。高剂量的NO-711（50 mg/kg）诱导共济失调，但既不产生LORR，也不丧失夹尾反应。NO-711（50 mg/kg）引起的细胞外GABA水平升高仅为269.7% ± 24.2%。与此相反，临床上使用的静脉麻醉药丙泊酚引起翻正反射和夹尾反应的丧失。在以前的研究中，我们报告说，丙泊酚诱导的麻醉是介导的，至少部分，由GABA和谷氨酸神经元。这些结果表明，全身麻醉作用可能是通过增强抑制性神经传递和抑制兴奋性神经传递的组合而诱导的。