The mechanism of general anesthesia investigated in the area of non-synaptic neural transmitting at the extracellular space in the brain: focusing on nitric oxide and dopaminergic system

戊巴比妥（PB）和氯胺酮（Ket）影响大脑中神经递质的浓度。据报道，PB通过减少乙酰胆碱（ACh）释放来降低细胞外一氧化氮（NO）浓度，而Ket则通过增加乙酰胆碱（ACh）释放来增加NO浓度。本研究通过体内微透析实验，探讨PB和Ket对大鼠纹状体NO释放的影响及NO与乙酰胆碱的关系。使用雄性Sprague-Dawley大鼠。将微透析探针插入右侧纹状体并灌注改良林格氏液。每隔15分钟采集一次样品，并注入高效液相色谱系统。大鼠活动自如，腹腔注射PB和Ket。灌注液中分别加入新斯的明（1、10 μM）和甲胺（100 μM）。对每种麻醉剂的钙和镁浓度进行调整，以影响乙酰胆碱的释放。PB降低了NO产物（NOx）， Ket增加了NO产物（NOx）。虽然灌注新斯的明对基线Nox浓度没有影响，但它在低浓度下减少了铅诱导的Nox还原，在高浓度下消除了它。无镁灌注对基线Nox浓度没有影响，而低镁浓度灌注对铅诱导的Nox还原有拮抗作用。甲胺和无钙灌注对基线Nox浓度和ket诱导的Nox升高没有影响。PB可能通过减少Ach的释放来减少NO的释放，而Ket可能不受Ach的调节而增加NO的释放。此外，我们进行了一系列的初步研究，结果表明全身麻醉剂可以改变细胞外空间的许多神经传递途径，作为一种非突触神经传递。不仅是众所周知的麻醉剂靶受体之一GABA_A，随着Nox释放的变化，gaba_b受体也可能作为全身麻醉剂的靶受体参与其中。少

Pentobarbital (PB) and ketamine (Ket) influence the concentration of neurotransmitters in the brain. PB has been reported to decrease the extracellular nitric oxide (NO) concentration through a decrease in acetylcholine (ACh) release, while Ket has been shown to increase the NO concentration via an increase in ACh release. Here, we investigated effects of PB and Ket on NO release and the relationship between NO and ACh in the rat striatum by in vivo microdialysis experiments. Male Sprague-Dawley rats were used. A microdialysis probe was inserted into the right striatum and perfused with modified Ringer’s solution. Samples were collected every 15 min and injected into an HPLC system. The rats were freely moving, and PB and Ket were administered intraperitoneally. Neostigmine (1 and 10 μM) and mecamylamine (100 μM) were added to the perfusate. Calcium and magnesium concentrations were modified for each anesthetic to influence Ach release. PB decreased NO products (NOx) while Ket increase … More d them. While perfusion with neostigmine showed no effect on baseline Nox concentrations, it diminished the PB-inducedNOx reduction at low concentrations and abolished it at high concentrations. Magnesium-free perfusion had no effect on baseline Nox concentrations, whereas perfusion at a low magnesium concentration antagonized the PB-induced Nox reduction. Mecamylamine and calcium-free perfusion had no effect on baseline Nox concentrations and Ket-induced Nox increases. PB may decrease NO release through reduction in Ach release, whereas Ket may increase NO release independent of Ach regulation.Moreover, we studied a series of preliminary investigations and the results suggested that general anesthetics could modify many pathways of neural transmitting in extracellular space as a non-synaptic neural transmission. Not only GABA_A, which is one of well-known target receptors of anesthetics, but also GABA_Breceptor would be involved in as a target of general anesthetics with the current results of changing in releases of Nox. Less