Role of 5-hydroxytryptamine in ketamine-induced hypothermia in the rat.

1. Intraperitoneal injection of graded doses of ketamine produced a dose-dependent fall in body temperature of rats. Similarly, intracerebral injection of much smaller doses produced hypothermia.2. Pretreatment of the rats with p-chlorophenylalanine (PCPA) greatly attenuated the hypothermic response to ketamine whereas the intraperitoneal injection of 5-hydroxytryptophan in PCPA-treated rats restored the hypothermic effect of ketamine.3. Depletion of the brain monoamines by reserpine completely prevented the ketamine-induced hypothermia. Treatment with sodium diethyldithiocarbamate (DEDTC), however, did not modify the hypothermic effect of ketamine.4. Pretreatment of the rats with pargyline potentiated the ketamine-induced hypothermia.5. Depletion of brain monoamines by reserpine in combination with inhibition of noradrenaline biosynthesis (DEDTC) resulted in a long lasting fall in temperature which was not modified by ketamine.6. When the ambient temperature was raised from 26 degrees C to 32 degrees C, ketamine-induced hypothermia was much reduced and superimposed on a hyperthermia which occurred in all animals.7. It is concluded that ketamine produces hypothermia in rats possibly through the release of 5-hydroxytryptamine in the hypothalamus and that this effect is similar in some respects to that produced by morphine in non-tolerant rats.