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The effect of the 5-hydroxytryptamine (5-HT) precursor 5-hydroxytryptophan (5-HTP) on the thermoregulatory responses of unanesthetized rats were assessed at three different ambient temperatures (Ta) of 8, 22 and 31 degrees C. Intraperitoneal administration of either 5-HTP alone or 5-HTP plus R04-4602 (the peripheral decarboxylase inhibitor) produced dose-dependent hypothermia at both Ta's of 8 and 22 degrees C. The hypothermia was brought about solely by a decrease in metabolic heat production at 8 degrees C Ta. At 22 degrees C Ta, the hypothermia was due to both a decrease in metabolic heat production and an increase in tail and footsole skin temperature. However, at 31 degrees C Ta, there were no changes in rectal temperature in response to either 5-HTP or 5-HTP plus R04-4602 application. The data suggest that an increase in 5-HT levels in brain decreases heat production and/or increase heat loss and leads to hypothermia in rats.
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