title: Nitrous oxide-induced hypothermia in the rat: acute and chronic tolerance.
abstract: Although inhalation of nitrous oxide (N2O) causes hypothermia in rats, there is a paucity of information as to whether tolerance develops to this effect. The purpose of this study was to determine whether tolerance to N2O hypothermia develops within a single administration as well as over repeated administrations. Temperature was measured telemetrically by implanting intraperitoneal thermal sensors/transmitters in male Long-Evans rats. Experimental rats received an initial 2-h exposure to 60% N2O and became hypothermic relative to controls breathing placebo gas. Only a few rats demonstrated evidence of acute tolerance over the 120 min. Over the next 10 days, the experimental rats received five additional 30-min exposures to 60% N2O and five 30-min exposures to placebo while the control rats received only placebo gas exposures. Chronic tolerance developed to N2O hypothermia over these repeated administrations. A test for Pavlovian drug conditioning found no evidence that conditioned temperature effects contributed to chronic tolerance development. In a second experiment, naive rats were given a 380-min exposure to 60% N2O and a 380-min exposure to placebo gas in a counterbalanced order. Acute tolerance did develop to N2O hypothermia, with the recovery of temperature beginning after a mean of 141 min of gas administration. Hence, both acute and chronic tolerance develop to N2O's hypothermic effects in rats.
authors.affiliation: Department of Pediatric Dentistry, University of Washington, Seattle 98195-7136, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Ramsay
authors.forename: K
authors.initials: K
authors.lastname: Omachi
authors.forename: B G
authors.initials: BG
authors.lastname: Leroux
authors.forename: R J
authors.initials: RJ
authors.lastname: Seeley
authors.forename: C W
authors.initials: CW
authors.lastname: Prall
authors.forename: S C
authors.initials: SC
authors.lastname: Woods
mesh_terms: D000280:Administration, Inhalation; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects; D004361:Drug Tolerance; D007035:Hypothermia / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D009609:Nitrous Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans