Discriminative stimulus effects of nitrous oxide in mice: comparison with volatile hydrocarbons and vapor anesthetics.

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.

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Abstract

The abuse-related behavioral effects produced by nitrous oxide (N₂O) gas have been suggested as being unique compared with other abused inhalants. The drug discrimination paradigm in animals can be used to study subjective effects of drugs in humans and to test this hypothesis. The goals of the present experiment were to establish N₂O discrimination in mice and to compare its discriminative stimulus effects with those of abused volatile vapors and vapor anesthetics. Sixteen B6SJLF1/J mice were trained to discriminate between 10 min of exposure to 60% N₂O+40% oxygen (O₂) and 10 min of exposure to 100% O₂. The time course of N₂O discrimination was examined, followed by cross-substitution testing with abused vapors, volatile anesthetics, ethanol, D-amphetamine, and 2-butanol. Mice acquired the ability to discriminate between N₂O and O₂ in 40 days. N₂O fully substituted for 10 min of exposure to 60% N₂O in a concentration-dependent manner. Full substitution required 7 min of 60% N₂O exposure, but the offset of stimulus effects following the cessation of exposure was more rapid. The aromatic hydrocarbon toluene almost fully substituted for N₂O. 1,1,1-Trichloroethane, methoxyflurane, isoflurane, and ethanol showed lesser degrees of substitution. D-amphetamine and the odorant 2-butanol did not substitute for N₂O. Given the varying degrees of incomplete substitution by test compounds, the discriminative stimulus properties of N₂O and, perhaps, its subjective effects in humans are probably not unique. As none of the inhalants tested fully mimicked N₂O, its overall effects may include one or more novel stimulus components.