Conditioned place aversion and self-administration of nitrous oxide in rats.

The rewarding/aversive effects of nitrous oxide (N2O) were evaluated using the place conditioning paradigm. Male Long–Evans rats (N=103) received a daily 40-min gas exposure for 8 consecutive days that alternated between two distinct chambers. A control group received placebo gas in both chamber types, while the N2O groups (8%, 15%, 30%, and 60% N2O) received four consistent pairings of N2O with one chamber type and four pairings of placebo gas with the other. A conditioned place aversion was found for the chambers that had been paired with 30% and 60% N2O. Place aversions were demonstrated during a 20-min test session on Day 9 when placebo gas was delivered to both chambers, and also during a 20-min test session on Day 10 when N2O was delivered to both chambers. A second study evaluated two novel methods of inhalant self-administration, one that used a forced-choice alternating gas environment and one that used a free-choice paradigm. Of four rats tested, two self-administered N2O, one rat avoided N2O, and one rat's behavior was consistent with neither self-administration nor avoidance. Availability of these methods will facilitate research on the neurobiological mechanisms underlying the rewarding and reinforcing effects of N2O and other abused inhalants.