Regional brain salicylate concentrations in afebrile and febrile rabbits.
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Biomedical subjects
Publications and source records attributed to R H Luff.
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1. The imino-dibenzyl drugs, imipramine and desipramine, which inhibit the uptake by neurones of noradrenaline, were injected into the lateral cerebral ventricles of cats and rabbits: changes in body temperature resulted which were different for the two species, but nevertheless closely resembled those following intraventricular injection of relatively large quantities of exogenous noradrenaline.2. The endogenous noradrenaline content of the hypothalamus in both species was reduced by repeated injections into the lateral ventricle of the methyl ester of DL-alpha-methyl-p-tyrosine: in animals so treated the hypothalamic content of 5-hydroxytryptamine was not significantly changed.3. Noradrenaline-depleted animals showed significantly reduced responses to intraventricular imipramine and desipramine. The diminished responses were primarily due to reduction in endogenous noradrenaline.4. These observations indicate that endogenous noradrenaline, present in the hypothalamus, can influence body temperature in cats and rabbits.
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1. Steady state fever has been produced in rabbits with a priming injection followed by a sustaining infusion of homologous plasma containing endogenous pyrogen (EP). This fever appears to last as long as the infusion continues.2. Intravenous salicylate given 1 h after the start of the EP infusion produced only a small antipyretic effect. The same dose of salicylate given 4 h after the start of an EP infusion resulted in rapid and progressive defervescence. Intermediate antipyretic responses were obtained when salicylate was administered intravenously 2 and 3 h after the start of an EP infusion.3. Less than 1% of the systemic dose, when injected into a lateral cerebral ventricle, produced a significantly smaller response at 1 h than at 4 h after the start of an EP infusion. At both these times the fall in temperature following the intraventricular salicylate injection was dose dependent, but the slope of the dose-response line was significantly steeper at 4 h than at 1 hour.4. It is suggested that salicylates produce their antipyretic effects by antagonizing the action of EP within the nervous system, and that the hypothalamic EP concentration falls during the course of an EP infusion.
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