Analysis of the reinforcing and subjective effects of different doses of nitrous oxide using a free-choice procedure.

The reinforcing and subjective effects of five doses of nitrous oxide (0, 10, 20, 30, 40% N(2)O in O(2)) were studied in 20 non-drug-abusers using a free-choice procedure. During each of five sessions, subjects sampled a dose of N(2)O and 100% O(2) (placebo) for 10 min each. Later they chose nine times, once every 5 min, among N(2)O (e.g. 'Agent A'), placebo (e.g. 'Agent B'), or a no-drug option. Mean preference ratios (N(2)O choices/[N(2)O choices+placebo choices]) and total N(2)O choice increased with increasing N(2)O dose. Individual preference ratios suggested that at least one active dose of N(2)O functioned as a reinforcer in 80% of subjects, and the doses that functioned as reinforcers varied across subjects. N(2)O choice was positively correlated with end-of-session and post-session ratings of N(2)O liking and of wanting to inhale N(2)O again, but not with ratings of those effects during sampling. Placebo was chosen significantly less than the no-drug option, even though both were 100% O(2). More robust reinforcing effects of N(2)O were observed in this subject population than in previous studies. Choice data emphasize the importance of examining a range of doses, and of examining those effects within-subject, when assessing reinforcing effects of drugs. Inclusion of the no-drug option eliminated the 'forced' choice of placebo, making preference ratios easier to interpret than in previous, forced-choice procedures. Reinforcing effects were more correlated with subjective effects assessed after the session than with subjective effects obtained while subjects were under the influence of the drug.