Nitrous oxide (N2O) is used as an anesthetic and is also abused, but the receptors responsible for its intoxicating effects are poorly understood. In mice trained to discriminate 60% N2O from oxygen, N2O produced concentration-dependent full substitution for itself, with full substitution requiring 7 minutes of exposure and rapid offset after cessation. The abused vapor toluene produced the most robust substitution, fully substituting for N2O in 7 of 8 subjects, suggesting shared neurochemical mechanisms. NMDA receptor open-channel blockers partially substituted, while GABAA agonists, opioids, and other drugs did not. No drug produced over 80% N2O-lever selection, indicating other neurochemical contributors remain unknown.
Nitrous oxide (N₂O) gas produces abuse-related behavioral effects that may differ from other inhalants. In a drug discrimination experiment, 16 mice were trained to distinguish between 10-minute exposure to 60% N₂O mixed with oxygen and pure oxygen. Mice learned this discrimination in 40 days. N₂O itself fully substituted for the training condition in a concentration-dependent manner, with full substitution requiring 7 minutes of exposure. The aromatic hydrocarbon toluene almost fully substituted for N₂O, while other compounds like 1,1,1-trichloroethane, methoxyflurane, isoflurane, and ethanol showed lesser substitution. D-amphetamine and the odorant 2-butanol did not substitute. The varying degrees of incomplete substitution suggest that N₂O's discriminative stimulus properties—and likely its subjective effects in humans—are probably not unique, though its overall effects may include novel components.