Changes in the hyperthermic responses of rats to daily injections of morphine and the antagonism of the acute response by naloxone.

Core temperatures of unrestrained male rats were measured by rectal probe over a 4-h period following seven daily subcutaneous injections of morphine sulphate in doses of 5, 20, or 80 mg/kg. With the smaller doses, rapid hyperthermia occurred and was maximal after 20 mg/kg; with 80 mg/kg, two of eight rats had immediate hypothermia, with the group response being a small, delayed hyperthermia. The results with repeated administration of morphine give statistical validity to earlier findings suggesting that peak hyperthermia increased and occurred progressively sooner after each injection of morphine. In groups of naive rats a single injection was given of saline or of 1, 10, or 40 mg naloxone hydrochloride per kilogram in saline. In these rats saline led to a slight increase in core temperature; when the first injection was one of the three doses of naloxone, no transient increase was seen. In nine other groups each of the three doses of naloxone was given 15 min before each of the morphine doses. All three doses of naloxone significantly reduced the hyperthermia induced by 5 and 20 mg morphine sulphate per kilogram, but this was less apparent in the group treated with 80 mg/kg, although naloxone at 40 mg/kg prevented any increase in temperature for over 3 h. The results obtained in this study demonstrate that morphine-induced temperature changes and perhaps stress-induced changes can be suppressed by naloxone.