Experimental nitrous oxide exposure as a model system for evaluating neurobehavioral tests

A recent study reported that a minimally suprathreshold dose of 20% nitrous oxide significantly affected performance on 3 of 9 computer-administered neurobehavioral tests. Performance decrements were observed in that study on 3 tests of psychomotor speed while other neurobehavioral functions such as visuospatial ability, verbal learning and mood were not significantly affected. The current study was undertaken to assess the reproducibility of these earlier results. Its experimental design was expanded to include an additional dose of the anesthetic and a more complex reaction time task implemented by the authors since the earlier study. Fifteen males aged 24-34 years were tested with the Neurobehavioral Evaluation System (NES) test battery on 4 separate occasions. An initial training session was followed by randomly presented control, 20%, and 40% drug sessions. Drug-induced decrements in performance were observed in the current study at the 20% dose for 2 of the 3 tests of psychomotor speed which had shown effects in the earlier study, and average decrement in performance on the third approached statistical significance in the current study (P = 0.055). Performance on a complex reaction time task was significantly affected at the low dose. The higher dose of nitrous oxide impaired performance on 8 of the 9 tests administered, and impairment on the ninth test was nearly significant (P = 0.055). Overall, these data are consistent with those in the previous study and with other reports that higher doses of nitrous oxide produce impairments in more cognitive CNS functions. Owing to its relative safety at low dosages, ease of administration, and ready acceptance by experimental subjects, nitrous oxide appears to be a useful model for evaluating the validity of neurobehavioral tests.