Prostaglandin synthetase inhibitors antagonize hypothermia induced by sedative hypnotics

Previous studies in our laboratory have demonstrated that inhibition of prostaglandin biosynthesis through pretreatment with aspirin and other prostaglandin synthetase inhibitors (PGSI) significantly reduces CNS sensitivity to a hypnotic dose of ethanol. Indomethacin, a potent PGSI, was administered to male LS, SS, and HS/Ibg mice (65 +/- 10 days of age) 15 min prior to administration of a hypnotic dose of ethanol or pentobarbital. Doses of indomethacin used were identical to those previously reported as optimally antagonizing ethanol-induced sleep. Another group received a vehicle-control injection, while a third group also received a control injection, but were placed in a incubator maintained at 30 +/ 1 degrees C. Body temperatures were recorded periodically for several hours. Both indomethacin and incubation significantly reduced hypothermia induced by ethanol and pentobarbital. Incubation increased sleep time after ethanol, but did not affect pentobarbital sleep time. These results suggest that the hypnotic and hypothermic effects of ethanol, although possibly mediated through prostaglandins, apparently are not causally linked.