Nitrous oxide is widely used for production of conscious sedation in clinical dentistry. This clinical application of low concentrations of nitrous oxide specifically for reduction of anxiety is unique to dentistry. Nitrous oxide also possesses prominent analgesic and weak anesthetic properties that have been widely studied. However, its anxiolytic effect has not been well investigate and the underlying mechanism(s) of action remain(s) unknown. Recent research suggests that an apparent anxiolytic effect of nitrous oxide is demonstrable in the mouse staircase test, a relatively new anxiety paradigm. This application proposes pilot experiments to determine the feasibility of future basic research into the mechanism of anxiolytic effect of nitrous oxide. The goals of this proposed research are to study 2 established and validated experimental paradigms (the social interaction test and the defensive burying test in rats): (1) a concentration-dependent anxiolytic effect of nitrous oxide and comparison with chlordiazepoxide (an anxiolytic standard) and morphine (an analgesic standard); and (2) sensitivity of the effects of these 3 drug challenges (nitrous oxide, chlordiazepoxide and morphine) to interaction with opioid and benzodiazepine receptor blockers. Carried to a successful conclusion, this proposed research will make possible further and more sophisticated investigations for characterization of the anxiolytic effect of nitrous oxide and elucidation of its mechanism(s) of action. The long term objective of this research is to continue a systematic analysis of the pharmacological properties of nitrous oxide. The findings of such research should advance our understanding of the pharmacology of nitrous oxide and contribute to more efficacious or judicious clinical use of nitrous oxide in dentistry and medicine.
