Nitrous oxide causes a regulated hypothermia: Rats select a cooler ambient temperature while becoming hypothermic

An initial administration of 60% nitrous oxide (N2O) evokes hypothermia in rats and if the administration continues for more than 1-2 h, acute tolerance typically develops such that the initial reduction in core temperature (Tc) reverses and Tc recovers toward control values. Calorimeter studies at normal ambient temperature indicate that hypothermia results from a transient reduction in heat production (HP) combined with an elevation in heat loss. Acute tolerance develops primarily due to progressive increases in HP. Our aim was to determine whether rats provided a choice of ambient temperatures would behaviorally facilitate or oppose N2O-induced hypothermia. A gas-tight thermally-graded alleyway (range, 6.7-37.0 °C) enabled male Long-Evans rats (n = 12) to select a preferred ambient temperature during a 5-hour steady-state administration of 60% N2O and a separate paired control gas exposure (order counterbalanced). Tc was measured telemetrically from a sensor surgically implanted into the peritoneal cavity > 7 days before testing. Internal LED lighting maintained the accustomed day:night cycle (light cycle 0700-1900 h) during sessions lasting 45.5 h. Rats entered the temperature gradient at 1100 h, and the 5-h N2O or control gas period did not start until 23 h later to provide a long habituation/training period. Food and water were provided ad libitum at the center of the alleyway. The maximum decrease of mean Tc during N2O administration occurred at 0.9 h and was −2.05 ± 0.25 °C; this differed significantly (p < 0.0001) from the corresponding Tc change at 0.9 h during control gas administration (0.01 ± 0.14 °C). The maximum decrease of the mean selected ambient temperature during N2O administration occurred at 0.7 h and was −13.58 ± 1.61 °C; this differed significantly (p < 0.0001) from the corresponding mean change in the selected ambient temperature at 0.7 h during control gas administration (0.30 ± 1.49 °C). N2O appears to induce a regulated hypothermia because the selection of a cool ambient temperature facilitates the reduction in Tc. The recovery of Tc during N2O administration (i.e., acute tolerance development) could have been facilitated by selection of ambient temperatures that were warmer than those chosen during control administrations, but interestingly, this did not occur.

Research Highlights►Rats select cooler ambient temperatures during nitrous oxide-induced hypothermia. ►Nitrous oxide causes a regulated hypothermia. ►Acute tolerance develops to nitrous oxide-induced hypothermia.