The effect of anesthetics on the release of neurotranmitters in freely moving rat hippocampus investigated with microdialysis technique.

用微透析法研究了全麻对大鼠海马神经递质释放的影响。在第一个实验中，我们研究了氯胺酮麻醉下海马细胞外液中去甲肾上腺素（NE）浓度的变化。在第二个实验中，使用自由活动的大鼠，研究了氯胺酮诱导的兴奋性和抑制性神经递质释放的变化。氯胺酮（5、20和80 mg/kg）对海马NE释放的基础水平无影响，但可阻断高浓度钾（60 mM）去极化引起的NE释放增加。NMDA受体阻断剂MK-801不能抑制氯胺酮（20、40和80 mg/Kg）诱导的NE释放增加。在第二个实验中，使用自由活动的大鼠，氯胺酮（10，40和100 mg/kg）对海马中的基础谷氨酸释放没有影响。由于抑制性递质GABA的含量太低，无论是高效液相色谱法（HPLC）还是荧光分光光度法（SPF）都无法检测到。采用更灵敏的酶循环法测定氯胺酮诱导GABA释放的变化.氯胺酮对高浓度钾（100 mM）去极化引起的谷氨酸释放增加的影响.其他类型的全身麻醉药，如巴比妥类，吸入麻醉和吗啡，诱导神经递质释放也将进行研究。

The effects of general anesthesia on the release of neurotransmitters were studied in the rat hippocampus by a microdialysis method. In the first experiments, we examined changes in norepinephrine (NE) concentration in hippocampal extracellular fluid under ketamine anesthesia. In the second experiments, using freely moving rats, changes in the release of excitatory and inhibitory neurotransmitters induced by ketamine were investigated. Ketamine (5,20 and 80 mg/kg) did not affect the basal level of NE release in the hippocampus, while it blocked the increase in NE release induced by depolarization with a high concentration of potassium (60mM). An NMDA receptor blocker, MK-801, did not inhibit the increase in NE release induced by ketamine (20,40 and 80 mg/Kg) administration. In the second experiments, using freely moving rats, ketamine (10,40 and 100 mg/kg) had no effect on basal glutamate release in the hippocampus. The inhibitory transmitter, GABA,could not be detected by either high-performace liqid chromatography (HPLC) or spectrophotofluoresence method (SPF) because levels were too low.On present research is focused on the following :1. Measuring the changes in GABA release induced by ketamine by a more sensitive method, the enzyme cycling method.2. Effects of ketamine on increased glutamate release evoked by depolarization with a high concentration of potassium (100mM).3. Neurotransmitter release induced by other types of general anesthetics, such as barbiturates, inhalation anesthesia and morphine, will also be investigated.