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

Abstract The 5-HT 7 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-HT 7 -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-HT 7 receptor antagonist reverses the hypothermic effect of 5-CT in guinea-pigs. The current study confirmed that the 5-HT 7 receptor antagonists, SB-269970 (1–30 mg/kg, i.p.) and SB-258719 (5–20 mg/kg, i.p.), but not the 5-HT 1A receptor antagonist, WAY 100635(0.1–1 mg/kg, s.c.), or the 5-HT 1B/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-HT 7 receptor null mutant mice. 5-CT (0.1–1 mg/kg, i.p.) significantly reduced rectal temperature in wildtype but not 5-HT 7 receptor knockout mice. This suggests that the hypothermic effects of 5-CT are mediated through the 5-HT 7 receptor. All procedures were carried out in accordance with the UK Animals (Scientific Procedures) Act (1986).