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

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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.