The proposed research examines acute and chronic tolerance to nitrous oxide (N2O) in human subjects. In two studies, subjects will initially be trained to respond when they detect, and subsequently feel pain in response to electrical tooth stimulation. In one double-blind cross-over experiment, N2O or placebo gas will be administered for 40 min, and the detection and pain thresholds monitored. Analgesia is expected to occur in all subjects and some are hypothesized to become acutely tolerant when N2O is administered. Rebound effects will be examined when the drug is withdrawn. Degree and incidence of acute tolerance will be related to rebound effects. In a second double-blind experiment, subjects will receive N2O in association with a distinct odor cue on 5 sessions occurring over 3 days. Tolerance to the analgesic effect is hypothesized to develop over the sessions, and a final test session will determine the role that conditioning plays in the expression of this tolerance. The findings have clinical significance for those administering and taking N2O; and they have theoretical importance for understanding the mechanisms of drug tolerance and possibly addiction using a human model.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29DA007391-05
Application #
2119908
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1991-07-01
Project End
1996-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Washington
Department
Pediatrics
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Ramsay, Douglas S; Leroux, Brian G; Rothen, Marilynn et al. (2005) Nitrous oxide analgesia in humans: acute and chronic tolerance. Pain 114:19-28
Ramsay, D S; Omachi, K; Leroux, B G et al. (1999) Nitrous oxide-induced hypothermia in the rat: acute and chronic tolerance. Pharmacol Biochem Behav 62:189-96
Dunlosky, J; Domoto, P K; Wang, M L et al. (1998) Inhalation of 30% nitrous oxide impairs people's learning without impairing people's judgments of what will be remembered. Exp Clin Psychopharmacol 6:77-86
Coldwell, S E; Kaufman, E; Milgrom, P et al. (1998) Acute tolerance and reversal of the motor control effects of midazolam. Pharmacol Biochem Behav 59:537-45
Ramsay, D S; Woods, S C (1997) Biological consequences of drug administration: implications for acute and chronic tolerance. Psychol Rev 104:170-93
Fiset, L; Leroux, B; Rothen, M et al. (1997) Pain control in recovering alcoholics: effects of local anesthesia. J Stud Alcohol 58:291-6
Yi, D K; Barr, G A (1995) The induction of Fos-like immunoreactivity by noxious thermal, mechanical and chemical stimuli in the lumbar spinal cord of infant rats. Pain 60:257-65
Geylikman, Y B; Artun, J; Leroux, B G et al. (1995) Effects of Le Fort I osteotomy on human gingival and pulpal circulation. Int J Oral Maxillofac Surg 24:255-60
Ramsay, D S; Brown, A C; Woods, S C (1992) Acute tolerance to nitrous oxide in humans. Pain 51:367-73