The Effects of Xenon and Nitrous Oxide Gases on Alcohol Relapse

Background In recent years, the glutamate theory of alcoholism has emerged as a major theory in the addiction research field and N‐methyl‐d‐aspartate (NMDA) receptors have been shown to play a major role in alcohol craving and relapse. The NMDA receptors are considered as the primary side of action of the anesthetic gases xenon (Xe) and nitrous oxide (N2O). Despite the rapid on/off kinetics of these gases on the NMDA receptor, a brief gas exposure can induce an analgesic or antireward effect lasting several days. The aim of this study was to examine the effect of both Xe and N2O on alcohol‐seeking and relapse‐like drinking behavior (measured as the alcohol deprivation effect) in Wistar rats. Methods We used 2 standard procedures—the alcohol deprivation model with repeated deprivation phases and the cue‐induced reinstatement model of alcohol seeking—to study the effect of 2 brief gas exposures of either Xe, N2O, or control gas on relapse‐like drinking and alcohol‐seeking behavior. Results Here, we show that exposure to Xe during the last 24 hours of abstinence produced a trend toward reduced ethanol intake during the first alcohol re‐exposure days. In addition, Xe gas exposure significantly decreased the cue‐induced reinstatement of alcohol‐seeking behavior. N2O had no effect on either behavior. Conclusions Xe reduces alcohol‐seeking behavior in rats and may therefore also interfere with craving in human alcoholics.