A dissociation between temperature regulation and fever in the rabbit.

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Abstract
The role of 5-hydroxytryptamine (5-HT) in temperature regulation and in fever in the rabbit was investigated. Intrahypothalamic microinjections of 5-HT in the conscious rabbit alters body temperature in a dose-dependent manner. Low doses (5.5 nmol) of 5-HT and control saline injections produce a small, non-significant increase in temperature, with a long latency. Doses of 14 nmol 5-HT produce a hyperthermia with a 45 min delay; while microinjections of 28 nmol result in a biphasic response; an initial short hypothermia is followed later by a hyperthermia. Depleting the rabbit''s brain of 5-HT by pretreatment with p-chlorophenylalanine (PCPA) fails to affect its body temperature at thermoneutral temperatures but significantly impairs the ability to thermoregulate against a cold stress. PCPA pretreatment did not impair the febrile response to bacterial pyrogen and prostaglandin E1. These results reveal a dissociation between the effects of 5-HT depletion on temperature regulation, and on fever. The site of action of 5-HT in temperature regulation must be proximal to the fever input, but distal to the convergence of peripheral and hypothalamic temperature inputs.