Effects of melatonin on both thermoregulatory responses and hypothalamic serotonin release were assessed in unanesthetized rats at three different ambient temperatures (Ta). Systemic administration of melatonin (30-120 mg/kg, i.p) caused a decrease in both colonic temperature and hypothalamic serotonin (5-HT) release in rats at both Ta 8 and 22°C. The hypothermia was brought about by a decrease in metabolic rate at Ta 8°C, whereas at Ta 22°C the hypothermia was produced by both a decrease in metabolic rate and an increase in cutaneous temperature. However, in the heat (Ta 31°C), neither thermoregulatory responses nor hypothalamic 5-HT release was affected by the same amount of administered melatonin. The melatonin-induced hypothermia and decreased 5-HT release in the hypothalamus were attenuated by selective depletion of brain 5-HT produced by intracerebroventricular injection of 5,7-dihydroxytryptamine. Furthermore, the melatonin-induced hypothermia was almost completely abolished by treatment with a 5-HT2A receptor agonist (DOI) or a 5-HT1A receptor antagonist [(-)-pindolol]. The data indicate that melatonin potentiates the 5-HT1A receptor activation in the hypothalamus and results in hypothermic effects which can be antagonized by the expected hyperthermic effect of DOI.
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