Differential acute tolerance development to effects of nitrous oxide in humans.
J P Zacny, A M Cho, D W Coalson, G Rupani, C J Young, J M Klafta, P A Klock, J L Apfelbaum
Neuroscience letters May 10, 1996 DOI: 10.1016/0304-3940(96)12626-4 via PubMed
Summary
AI-generated from the abstractInhaling nitrous oxide at increasing doses (10–40%) reduces pain intensity and the bother of pain from cold-water immersion, but this analgesic effect weakens over a 120-minute inhalation period (acute tolerance). Some pleasant subjective effects, such as elation and drug liking, also show acute tolerance. Other subjective effects and psychomotor impairment do not change significantly during the inhalation period, indicating no acute tolerance for those measures. The differing patterns of tolerance suggest that distinct neurochemical systems may mediate different effects of nitrous oxide.
Study at a glance
| Characteristics | Prospective, randomized, crossover, double-blind study Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Volunteers |
| Intervention | Nitrous oxide |
| Dose | 0, 10, 20, 30, and 40% nitrous oxide in oxygen |
| Duration | 120 min inhalation |
| Key finding | Acute tolerance develops to the analgesic and some hedonic subjective effects of nitrous oxide but not to other subjective effects or psychomotor impairment. |
Abstract
The analgesic, subjective, and psychomotor effects of 0, 10, 20, 30, and 40% nitrous oxide in oxygen were studied in 10 volunteers to determine if acute tolerance developed differentially to these variables. In this prospective, randomized, crossover, double-blind study, volunteers inhaled either placebo (100% oxygen) or one of the aforementioned doses of nitrous oxide for 120 min. During this period, volunteers immersed their non-dominant forearm, for 3 min, in ice-cold water at 25, 70 and 115 min from the onset of the inhalation. At other prescribed time intervals throughout the session, mood and psychomotor performance were assessed. Subjects reported less pain intensity from the cold-water stimulus and reported the pain bothered them less as a function of increasing nitrous oxide dose; in addition, this analgesia was significantly less as the inhalation period progressed (i.e., acute tolerance). Some subjective effects of nitrous oxide that could be considered hedonic in nature (elation, drug liking) also showed evidence of acute tolerance. In contrast, other subjective effects and the psychomotor-impairing effects of nitrous oxide did not change significantly during the inhalation period (i.c., no acute tolerance). The differential acute tolerance observed in this study suggests that different effects of nitrous oxide may be mediated by different neurochemical substrates.