title: Ambient temperature influences core body temperature response in rat lines bred for differences in sensitivity to 8-hydroxy-dipropylaminotetralin.
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 degrees C, and core temperature was measured by radiotelemetry. For both lines, the thermic response to acute 8-OH-DPAT was greatest at 10.5 degrees C and decreased in magnitude as ambient temperature increased to 30 degrees C, consistent with hypothermia. HDS rats displayed a greater hypothermic response than LDS rats at 10.5, 24, and 30 degrees C. At 37.5 degrees 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 degrees C, but increased in HDS rats treated with 0.50 mg/kg 8-OH-DPAT at 30 and 37.5 degrees C. This pattern was reversed in HDS rats following 8-OH-DPAT challenge at 24 degrees C, suggesting that a compensatory thermoregulatory response accounts for changes in the hypothermic response to chronic 8-OH-DPAT.
authors.affiliation: Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, Illinois 60637, USA. acnichol@midway.uchicago.edu
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Nicholas
authors.forename: Lewis S
authors.initials: LS
authors.lastname: Seiden
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D001833:Body Temperature Regulation; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012965:Sodium Chloride; D013696:Temperature
chemical_list: D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012965:Sodium Chloride; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin