Rebound electroencephalographic responses to nitrous oxide exposure in men

Nitrous oxide (N₂O) may elicit antidepressant effects after its elimination from the brain. We sought to investigate whether short-term administration of N₂O triggers power within the delta (0.5-4 Hz) and/or theta (4-7 Hz) frequency ranges in the electroencephalogram (EEG) after it's administration, as we have recently seen such rebound effects to N₂O in studies conducted on mice. Twenty healthy male participants were randomly allocated to receive 50% N₂O either continuously for 20 min (continuous group) or in two 10-min inhalations (repeated group) with 19-channel EEG. Median-averaged power spectral densities (PSDs) were calculated subject-, electrode-, and state-wise. Group-level data are topographically plotted and significant changes within specific frequency ranges for each condition are highlighted. The subjective effects in response to N₂O were studied with questionnaires. Fourteen participants completed the study (n = 7 participants/group). Spectrograms showed that the EEG transitions between N₂O and its withdrawal were extremely rapid in both groups and the effects remained stationary during specific states. Power in high-frequency bands (gamma) generally enhanced during N₂O administration along with power reductions in beta (and alpha) frequencies. Power in specific theta, but not delta, frequencies increase after the cessation of N₂O in several electrodes. However, direct comparison of the rebound EEG between the two treatment groups revealed negligible differences. Short-term administration of N₂O evokes increase of power in theta frequency, but not delta, band power upon gas withdrawal.NEW & NOTEWORTHY This study specifically addressed rebound EEG alterations within slow-wave frequency range upon withdrawal from N₂O in awake healthy participants. Short-term administration of N₂O increased power in theta, but not delta, frequency range upon gas withdrawal and this effect was readily reproduced with repeated dose.