5-hydroxytryptamine receptors in the hypothalamus mediate thermoregulatory responses in rabbits

Summary 1. The effects of microinjection of 5-hydroxytryptamine (5-HT) or its antagonists methysergide (a 5-HT₁ receptor antagonist), cyproheptadine (a mixed 5-HT₁/5-HT₂ receptor antagonist), or ketanserin (a 5-HT₂ receptor antagonist) into the preoptic anterior hypothalamus on thermoregulatory responses were assessed in conscious rabbits at different ambient temperatures (T_a). 2. Intrahypothalamic injection of 5-HT caused dose-dependent hypothermia in rabbits when the T_a was 2°C and 22°C. At 2°C the hypothermia was due to decreased metabolism, whereas at 22°C the hypothermia was due to increased peripheral blood flow and increased respiratory evaporative heat loss. 3. In contrast, administration of either cyproheptadine, methysergide or ketanserin into the 5-HT-sensitive sites in the preoptic anterior hypothalamus caused dose-dependent hyperthermia in rabbits when the T_a was 2°C, 22°C and 32°C. At 2°C the hyperthermia was due to increased metabolism, whereas at 32°C the hyperthermia was due to decreased peripheral blood flow and decreased respiratory evaporative heat loss. At 22°C, the hyperthermia was due to increased metabolism and decreased peripheral blood flow. 4. For a given intrahypothalamic dose (e.g.15–20 g), either methysergide, cyproheptadine or ketanserin produced the same degree of rectal temperature elevation (e.g. about 1.4°C) in rabbits. Thus, there did not appear to be any association between hypothalamic 5-HT receptor types and thermoregulation. 5. However, the present results suggest that hypothalamic 5-HT receptors mediate thermoregulatory responses in the rabbit. Activation of hypothalamic 5-HT receptors decreases heat production and increases heat loss, whereas inhibition of hypothalamic 5-HT receptors increases heat production and decreases heat loss in the rabbit.This study was supported by grants from the National Science Council of the Republic of China.Send offprint requests to S. J. Won at the above address