The hypothermic effect of 5-CT in mice is mediated through the 5-HT7 receptor

The 5-HT7 receptor is a recent addition to the 5-HT receptor family and to date there is no clear idea as to its potential role in the CNS. The receptor has been mapped by in situ hybridization and 5-HT7-like immunoreactivity and has been detected in discrete areas of the brain. including the hypothalamus (Oliver et al., 1999). This suggests the receptor may be involved in temperature regulation and Hagan et al. (2000) have shown that a selective 5-HT7 receptor antagonist reverses the hypothermic effect of 5-CT in guinea-pigs. The current study confirmed that the 5-HT7 receptor antagonists, SB-269970 (1-30 mg/kg, i.p.) and SB-258719 (5-20 mg/kg, i.p.), but not the 5-HT7 receptor antagonist, WAY 100635(0.1-1 mg/kg, s.c.), or the 5-HT1B/D antagonist, GR127935 (1.25-5 mg/kg, i.p.), reversed the hypothermic effect of 5-CT in mice. In addition the effect of 5-CT on body temperature was examined on 5-HT7 receptor null mutant mice. 5-CT (0.1-1 mg/kg, i.p.) significantly reduced rectal temperature in wildtype but not 5-HT7 receptor knockout mice. This suggests that the hypothermic 1 effects of 5-CT are mediated through the 5-HT7 receptor. All procedures were carried out in accordance with the UK Animals (Scientific Procedures) Act (1986). (C) 2003 Elsevier Science Ltd. All rights reserved.