Temperature responses in rats after acute and chronic administrations of caffeine.

Acute administrations (IP) of caffeine produced dose-dependent changes in the body temperature of rats. Low doses (12.5 and 25 mg/kg) induced hyperthermia soon after drug administration, while high doses (50 and 100 mg/kg) produced maximal hypothermia approximately 2 hr later. The acute effects of caffeine were also dependent on ambient temperature. The hyperthermic and hypothermic responses were attenuated and blocked, respectively, in rats maintained at 32 degrees C. At 4 degrees C, the hypothermic response was exacerbated, and the hyperthermic response was absent. Tolerance rapidly developed to the hypothermic actions of caffeine when rats were administered the drug over 28 days. Following the emergence of tolerance, hyperthermia was observed in rats given 50 mg/kg of caffeine. The hyperthermic responses to the low doses of caffeine were not altered by the frequency of drug administration. Both the acute and chronic effects of caffeine on thermoregulation are not unlike those found for morphine. Possible mechanisms of action underlying the thermoregulatory effects of caffeine are discussed.