5-HT receptors and hyper- or hypothermia: Elucidation by catecholamine antagonists injected into the cat hypothalamus

Abstract

The receptor mechanisms in the hypothalamus and preoptic area which mediate thermoregulatory changes produced by serotonin (5-HT) were examined in the unrestrained cat. Stainless steel guide tubes were implanted just above the rostral diencephalon or preoptic area in each of twelve cats. 5-HT in a dose of 1.5 to 10.5 μg was micro-injected in a volume of 0.75 to 1.5 μl into a total of 256 test sites in the hypothalamus. An individual site at which 5-HT evoked a rise or a fall in core temperature of ⩾ 0.5°C within 30 min was considered to be reactive to the indoleamine. Within such a region of maximum sensitivity, i.e., the cat's anterior hypothalamic, preoptic area (AH/POA), either norepinephrine (NE) or dopamine (DA) micro-injected in a dose of 2.33 to 14.0 μg in similar volumes evoked only a dose-dependent decline in the body temperature of the cat. 5-HT was found to cause either hyper- or hypothermia. The direction of temperature change caused by 5-HT was dependent principally upon the neuroanatomical locus of injection. Each of the 5-HT reactive sites was characterized pharmacologically by their pre-treatment with phentolamine (PHT), d-butaclamol (BUTAC) or methysergide (METHY) in doses of 1.0 to 10.0 μg. At the most rostral sites in POA, the catecholamine receptor antagonists selectively delayed the onset of the 5-HT hypothermia and limited the magnitude of the response. Within sites located in the AH in which 5-HT induced only a rise in body temperature, prior treatment of the site with the catecholamine receptor antagonists PHT or BUTAC failed to modify the response. These results indicate that 5-HT in producing hypothermia not only may saturate the 5-HT receptor sites but also may be taken up by catecholamine receptors which mediate the diencephalic heat loss pathway.