Effect of cycloheximide on temperature regulation in rats.

The effect of cycloheximide, an inhibitor of protein synthesis, on temperature regulation in afebrile rats was studied to determine whether its reported antipyretic effect might be attributable to a non-specific antimetabolic effect. Within 60 min after administration of cycloheximide (5 mg/kg IP) to female rats at ambient temperatures of 34, 25 and 15 degrees C, a significant decrease in colonic temperature was observed as compared with control rats administered saline IP. Measurements of rate of oxygen consumption showed that cycloheximide (5 mg/kg IP) significantly depressed the ability of rats to increase their heat production during a cold stress (15 degrees C). In the cold the rate of oxygen consumption increased 8.7 +/- 0.8 ml/min/kg0.75 in the control rats but only 1.8 +/- 0.9 ml/min/kg0.75 in the cycloheximide-treated rats. Since the thermoregulatory changes accompanying cold stress are similar to those observed during the genesis of fever, these data suggest that cycloheximide may have a general depressant effect on heat production rather than a specific antipyretic effect.