Bitonic dose–response functions for reinforcing and self-reported effects of nitrous oxide in humans

Abstract

The reinforcing and self-reported effects of nitrous oxide (10%, 30%, and 50% N 2O in O 2) were examined in 13 humans. During each of three sessions, subjects sampled one dose of N 2O and 100% O 2 (placebo) for 10 min each, separated by 30-min recovery periods. The agents were identified by letter code, and later in the session, subjects chose nine times, once every 5 min, among N 2O (e.g., “Agent A”), placebo (e.g., “Agent B”), or “neither” (also 100% O 2, identified as “drug-free air”). Self-reported and psychomotor effects were measured at various times. Dose–response functions varied across subjects and included bitonic, monotonic increasing, monotonic decreasing, U-shaped, and flat dose–response functions for reinforcing and/or self-reported effects. For subjects who showed bitonic reinforcing effects, the descending limb of the dose–response function could not be attributed to behavioral impairment. This study replicates previous studies showing dose-dependent effects of N 2O, as well as between-subject variability in N 2O effects. Bitonic dose–response functions for some subjects extend the generality of the phenomenon of bitonicity of drug effects to N 2O effects in humans.