Serotonin and thermoregulation: old and new views

An overview is presented of the evidence favouring a pivotal role for serotoninergic neurons in the diencephalon's control system for body temperature. 1. Morphological investigations of the anterior hypothalamus reveal that 5-HT injected locally into this thermosensitive zone evokes a hyperthermia in virtually all species. Pharmacological blocking agents of serotoninergic receptors antagonize the 5-HT-induced rise in an animal's temperature. 2. Further, the destruction of serotoninergic neurons in the anterior hypothalamic pre-optic area of a rat or monkey severely impairs the heat production responses during cold stress. 3. In addition, the release of 5-HT from anterior hypothalamic tissue is enhanced significantly when the animal is exposed to a cold environmental temperature, and subsequently shivers, vasoconstricts and conserves heat. 4. New observations are described which show that 5-HT may elicit a fall in temperature as a result of the: (1) overloading of 5-HT receptor sites in the anterior hypothalamus; and/or (2) occupation by 5-HT of either noradrenergic or dopaminergic receptors, or both classes of catecholamine receptors which are believed to mediate the hypothalamic pathways for heat loss. 5. Finally, new data also implicate neuronal 5-HT, again only within the anterior hypothalamic pre-optic area, in the cellular mechanism which triggers a fever in response to a bacterial challenge. Thus, the serotoninergic neurons underlying the rostral hypothalamic temperature controller are responsible not only for the defense of an animal's body temperature during exposure to cold, but also for initiating the shift in the temperature "set-point" during a febrile episode.