Abstract

Agonist-induced decrease in core body temperature has commonly been used as a measure of serotonin1A (5-HT_1A) receptor sensitivity in mood disorder. The thermoregulatory basis for 5-HT_1A receptor agonist-induced temperature responses in humans and rats remains unclear. Therefore, the influence of ambient temperature on 5-HT_1A receptor-mediated decreases in core body temperature were measured in rat lines bred for high (HDS) or low (LDS) sensitivity to the selective 5-HT_1A receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT). HDS and LDS rats were injected with either saline, 0.25 or 0.50 mg/kg 8-OH-DPAT at ambient temperatures of 10.5, 24, 30, or 37.5°C, and core temperature was measured by radiotelemetry. For both lines, the thermic response to acute 8-OH-DPAT was greatest at 10.5°C and decreased in magnitude as ambient temperature increased to 30°C, consistent with hypothermia. HDS rats displayed a greater hypothermic response than LDS rats at 10.5, 24, and 30°C. At 37.5°C, LDS rats showed a lethal elevation of temperature in response to 0.50 mg/kg 8-OH-DPAT. All thermic responses to 8-OH-DPAT, including the lethality, were effectively blocked by pretreatment with the 5-HT_1A receptor antagonist WAY100635, suggesting line differences in thermoregulatory circuits that are influenced by 5-HT_1A receptor activation. Following repeated injection of 8-OH-DPAT, the magnitude of the hypothermic response decreased in both lines at 10.5°C, but increased in HDS rats treated with 0.50 mg/kg 8-OH-DPAT at 30 and 37.5°C. This pattern was reversed in HDS rats following 8-OH-DPAT challenge at 24°C, suggesting that a compensatory thermoregulatory response accounts for changes in the hypothermic response to chronic 8-OH-DPAT.