Excitatory and inhibitory actions of isoflurane on the cholinergic ascending arousal system of the rat
Excitatory and inhibitory actions of isoflurane on the cholinergic ascending arousal system of the rat
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DOI：
10.1097/00000542-200601000-00018
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发表时间：
2006-01-01
期刊：
影响因子：
8.8
通讯作者：
Higuchi, T
中科院分区：
文献类型：
--
作者：
Dong, HL;Fukuda, S;Higuchi, T
背景：已知胆碱能唤醒系统严格调节意识状态。本研究的目的是利用体内脑内微透析确定异氟烷对胆碱能唤醒系统内重要核团的抑制性或兴奋性神经递质流出的影响。方法：下丘脑后部 (PH)、基底前脑 (BF) 和体感皮层中谷氨酸、γ-氨基丁酸 (GABA) 或乙酰胆碱的流出在清醒状态和0.5-2.0最小肺泡浓度(MAC)异氟烷麻醉下，使用脑内微透析检测大鼠(SHIF)。在这两种条件下还检查了α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和N-甲基-天门冬氨酸的基底内灌注对皮质乙酰胆碱流出的影响。结果：异氟醚对PH中的谷氨酸和GABA流出没有影响，而在BF中，它剂量依赖性地增加谷氨酸流出并减少GABA流出。在 S1BF 中观察到在 1.0 MAC 时谷氨酸流出量短暂增加，在 0.5-1.5 MAC 时 GABA 减少。异氟烷剂量依赖性地减少 S1BF 中的乙酰胆碱流出。在 0.75 MAC 异氟烷麻醉期间，用 AMPA 灌注 BF 增加了 S1BF 中的乙酰胆碱流出，并通过脑电图激活，表明异氟烷对 BE 中的 AMPA 受体具有抑制作用。然而，N-甲基-Daspartate 对这些参数没有影响。结论：异氟烷在胆碱能唤醒系统中同时诱导兴奋和抑制作用。异氟醚对 BF 的主要抑制作用超过其兴奋作用，将导致 S1BF 中乙酰胆碱流出量的减少。
Background: The cholinergic arousal systems are known to critically regulate the state of consciousness. The aim of this study was to determine the effect of isoflurane on the inhibitory or excitatory neurotransmitters efflux in important nuclei within the cholinergic arousal system using in vivo intracerebral microdialysis.Methods: The efflux of glutamate, gamma-aminobutyric acid (GABA), or acetylcholine in the posterior hypothalamus (PH), the basal forebrain (BF), and the somatosensory cortex (SHIF) of rats was detected using intracerebral microdialysis under an awake condition and at 0.5-2.0 minimum alveolar concentration (MAC) isoflurane anesthesia. The intrabasalis perfusion of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-Daspartate on the cortical acetylcholine effluxes was also examined under both conditions.Results: Isoflurane had no influence on the glutamate and GABA efflux in the PH, whereas in the BF, it dose-dependently increased glutamate efflux and decreased GABA efflux. A transient increase in glutamate efflux at 1.0 MAC and a decrease in GABA at 0.5-1.5 MAC were observed in the S1BF. Isoflurane dose-dependently decreased acetylcholine efflux in the S1BF. Perfusion of the BF with AMPA increased acetylcholine efflux in the S1BF with electroencephalographic activation during 0.75 MAC isoflurane anesthesia, suggesting an inhibitory action of isoflurane on AMPA receptors in the BE However, N-methyl-Daspartate had no effect on these parameters.Conclusion: isoflurane induces both excitatory and inhibitory actions in the cholinergic arousal system. The predominant inhibitory action of isoflurane over its excitatory action at the BF would result in the decrease in the acetylcholine efflux in the S1BF.