|Budget Amount *help
¥29,500,000 (Direct Cost: ¥29,500,000)
Fiscal Year 1986: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1985: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1984: ¥25,000,000 (Direct Cost: ¥25,000,000)
We firstly documented the acute development of tolerance to the CNS actions of nitrous oxide in cats: the CNS actions of nitrous oxide attenuated by a prolonged exposure. The present study consisted of (1) the neurophysiological and (2) the neurochemical studies to clarify the underlying mechanisms of its development.
1. Neurophysiologic studies: Nitrous oxide, 75 % in oxygen, induced 2-4 Hz high voltage slow waves in EEG in freely moving cats or halothane-oxygen anesthesia in man. These slow waves, however, disappeared after 2-3 hours, and awakefulness sleep cycle or the EEG pattern of halothane-oxygen anesthesia appeared. Nitrous oxide, when given to cats anesthetized with high dose of enflurane, enhanced the reticular neural firing for the 30 min, but this action subsided gradually. The anticonvulsant action of nitrous oxide, which was noted when it was given to the enflurane-induced epileptoid cats or amygdaloid kindled cats, attenuated after 30-60 min of administration. Nitrous oxide supressed the somato-sensory evoked potentials, which was augmented by deep enflurane anesthesia in cats. This suppressive action also subsided in 60-90 min of administration. In contrast to all findings mentioned above, the nitrous oxide analgesia was not tolerated for 120 min of administration in rats. All these indicate that (1) nitrous oxide affects different neurons and /or transmitters differently, and (2) different CNS functions are involved differently in both the time course and the nature.
2. Neurochemical studies: Nitrous oxide, 75 % in oxygen for 120 min, did not change the total-brain content of noradrenaline, dopamine, and 5HT, but increased those of DOPAC and HVA at 30 min of exposure in rats. These, however, decreases back to the control level thereafter, and increased again at 12 hours. The changes of catecholamine metabolism, thus, did not correlate with any of time courses of acute development of tolerance to the CNS actions of nitrous oxide.