The neurochemical basis for the development of acute tolerance to nitrous oxide

为了阐明急性氧化亚氮耐受发生的神经化学基础，采用脑微透析方法研究了氧化亚氮对大鼠大脑皮层氨基酸神经递质释放的影响。采用高效液相色谱法测定吸入75%氧化亚氮时和吸入4 h后的胞外氨基酸含量。兴奋性神经递质谷氨酸的释放在给予氧化亚氮期间和之后没有显著变化。然而，个体谷氨酸水平在吸入一氧化二氮后1或2小时内显著降低或升高；这些变化在停止使用氧化亚氮2小时后没有恢复。抑制神经递质γ氨基丁酸和甘氨酸的释放在氧化亚氮处理期间和处理后均呈下降趋势。非递质氨基酸，如谷氨酰胺、天冬酰胺、牛磺酸和丙氨酸，显示出与抑制性神经递质相同的趋势。在这项研究中，氧化亚氮对大脑皮层的神经递质释放没有明显影响。然而，对谷氨酸释放的影响是单独标记的。此外，这些影响在停止氧化亚氮2小时后仍未消失。这些发现表明，氧化亚氮可能影响谷氨酸神经传递；尽管停止使用这种药物，这些效果仍然存在。急性耐受性的发生与谷氨酸等神经递质释放的变化之间的关系有待进一步研究。

To clarify the neurochemical basis for the development of acute tolerance to nitrous oxide, the effects of nitrous oxide on the release of amino acids neurotransmitters in rat cerebral cortex were studied using brain microdialysis. The contents in extracellar amino acids during and after the 4 hours of inhalation of 75% nitrous oxide were measured with high performance liquid chromatography.The release of excitatory neurotransmitter, glutamate, did not significantly change during and after the administration of nitrous oxide. However, the individual glutamate levels markedly decreased or increased within 1 or 2 hours of inhalation of nitrous oxide ; these changes did not restore 2 hours after the cessation of nitrous oxide. The release of inhibitory neurotransmitters, such as gamma amino butyric acid and glycine, showed the tendency of decrease during and after the administration of nitrous oxide. The non transmitter amino acids, such as glutamine, asparagines, taurine, and alanine, revealed the same tendency as the inhibitory neurotransmitters.In this study, nitrous oxide did not apparently affect the neurotransmitter release in the cerebral cortex. However, the effects on the release of glutamate were marked individually. Moreover, these effects did not disappear 2 hours after stopping of nitrous oxide. These findings suggested that nitrous oxide might affect the glutamate neurotransmission ; these effects persisted despite of cessation of this agent. Further studies are needed to elucidate the relationship between the development of acute tolerance and the changes of neurotransmitter release such as glutamate.