Robust thermoregulatory overcompensation, rather than tolerance, develops with serial administrations of 70% nitrous oxide to rats

► Rats were tested for hypothermic magnitude during 70% nitrous oxide (N2O) inhalation. ► Hypothermia-sensitive and -insensitive groups received 12 subsequent N2O exposures. ► Core temperature, heat production and heat loss were measured in all sessions. ► After repeated N2O exposures, both groups became hyperthermic during N2O inhalation. ► Hyperthermia (via higher heat production) developed faster in the insensitive rats.