Abstract
Agonist-induced decrease in core body temperature has commonly been used as a measure of serotonin1A (5-HT1A) receptor sensitivity in mood disorder. The thermoregulatory basis for 5-HT1A receptor agonist-induced temperature responses in humans and rats remains unclear. Therefore, the influence of ambient temperature on 5-HT1A receptor-mediated decreases in core body temperature were measured in rat lines bred for high (HDS) or low (LDS) sensitivity to the selective 5-HT1A 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-HT1A receptor antagonist WAY100635, suggesting line differences in thermoregulatory circuits that are influenced by 5-HT1A 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.
Footnotes
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This study was supported by a grant from the National Institute of Mental Health (MH-11191).
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DOI: 10.1124/jpet.102.045088
- Abbreviations:
- 5-HT1A
- 5-hydroxytryptamine 1A
- 8-OH-DPAT
- (±) 8-hydroxy-dipropylaminotetralin HBr
- HDS
- high 8-OH-DPAT-sensitive
- LDS
- low 8-OH-DPAT-sensitive
- WAY100635
- N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride
- Received October 3, 2002.
- Accepted December 6, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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