Initial administration of ≥60% nitrous oxide (N2O) to rats promotes hypothermia primarily by increasing whole-body heat loss. We hypothesized that the drug promotes heat loss via the tail and might initially inhibit thermogenesis via brown adipose tissue (BAT), major organs of thermoregulation in rodents. Following repeated administrations, N2O inhalation evokes hyperthermia underlain by increased whole-body heat production. We hypothesized that elevated BAT thermogenesis plays a role in this thermoregulatory sign reversal. Using dual probe telemetric temperature implants and infrared (IR) thermography, we assessed the effects of nine repeated 60% N2O administrations compared to control (con) administrations on core temperature, BAT temperature, lumbar back temperature and tail temperature. Telemetric core temperature, telemetric BAT temperature, and IR BAT temperature were reduced significantly during initial 60% N2O inhalation (p≤0.001 compared to con). IR thermography revealed that acute N2O administration unexpectedly reduced tail temperature (p=0.0001) and also inhibited IR lumbar temperature (p<0.0001). In the 9th session, N2O inhalation significantly increased telemetric core temperature (p=0.007) indicative of a hyperthermic sign reversal, yet compared to control administrations, telemetric BAT temperature (p=0.86), IR BAT temperature (p=0.85) and tail temperature (p=0.47) did not differ significantly. Thus, an initial administration of 60% N2O at 21°C may promote hypothermia via reduced BAT thermogenesis accompanied by tail vasoconstriction as a compensatory mechanism to limit body heat loss. Following repeated N2O administrations rats exhibit a hyperthermic core temperature but a normalized BAT temperature, suggesting induction of a hyperthermia-promoting thermogenic adaptation of unknown origin.
Keywords: Addiction; Allostasis; Drug tolerance; Dysregulation; Homeostasis; Infrared thermography; Physiological adaptation; Telemetry; Thermoregulation.
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