Nitrous oxide and xenon increase noradrenaline release in the cerebral cortex in vivo and in vitro

Noradrenaline in the central nervous system plays an important role in regulating physiological functions, and is a key mechanistic component of general anesthesia. The purpose of this present study was to determine if nitrous oxide and xenon modulate noradrenaline release in the cerebral cortex. We performed a series of in vivo and in vitro experiments in rats. For the in vivo experiments, noradrenaline release was measured by microdialysis in the prefrontal cortex with exposure to 0, 30 or 60% nitrous oxide. For the in vitro experiments, noradrenaline release was measured from cerebrocortical slices before and after incubation with 0, 15, 30, or 60% nitrous oxide in Ca(2+)-containing buffer, Ca(2+)-free buffer, or in Ca(2+)-containing buffer with 10(-6)M tetrodotoxin (TTX). For the in vivo and in vitro experiments 60% xenon was also used. In the in vivo experiment, following exposure to nitrous oxide, noradrenaline release concentration-dependently increased. In the in vitro experiment, under Ca(2+)-containing conditions, noradrenaline release from cerebrocortical slices increased significantly during exposure to nitrous oxide in a concentration-dependent manner. Under Ca(2+)-free conditions, 60% nitrous oxide produced a significant release of noradrenaline. There were no significant differences in nitrous oxide-increased noradrenaline release between with and without TTX. Xenon also significantly increased noradrenaline release in the prefrontal cortex and from the cerebrocortical slices. The nitrous oxide-induced increase in noradrenaline release may be due to both excitation of the locus coeruleus-noradrenergic neuron and direct stimulation of its axon terminals.