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

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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.