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.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004878:Ergotamine / Q000494:pharmacology; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects; D007035:Hypothermia / Q000139:chemically induced*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007649:Ketamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008784:Methysergide / Q000494:pharmacology; D009638:Norepinephrine / Q000096:biosynthesis; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D013696:Temperature; D013859:Thiocarbamates / Q000494:pharmacology
D013859:Thiocarbamates; D012701:Serotonin; D007649:Ketamine; D012110:Reserpine; D010293:Pargyline; D006916:5-Hydroxytryptophan; D004878:Ergotamine; D010134:Fenclonine; D009638:Norepinephrine; D008784:Methysergide