Evidence that 5-HT2A receptors are not involved in 5-HT-mediated thermoregulation in mice

To determine the role of 5-hydroxytryptamine2A (5-HT2A) receptors in 5-HT-mediated thermoregulation in mice, we studied the effects of a 5-HT2A receptor agonist and 5-HT2A receptor antagonists on the body temperature, and the effects of selective 5-HT2A receptor and nonselective 5-HT receptor antagonists on hypothermia induced by 5-hydroxytryptophan (5-HTP). (+/-)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2A receptor agonist, did not change body temperature in mice at doses of 1 and 5 mg/kg, intraperitoneally (IP), which induced head twitch response. Three 5-HT2A receptor antagonists, ketanserin (1 mg/kg, orally), ritanserin (1 and 10 mg/kg, orally), and DV-7028 (10 mg/kg, orally), also failed to alter body temperature, although these three 5-HT2A receptor antagonists at > or = 1 mg/kg, orally, inhibited head twitch response induced by 5-HTP (200 mg/kg, IP), a precursor of 5-HT. Ketanserin (1 mg/kg, orally), ritanserin (1 and 10 mg/kg, orally), and DV-7028 (10 mg/kg, orally) did not inhibit hypothermia induced by 5-HTP (200 mg/kg, IP). A nonselective 5-HT receptor antagonist, methysergide (1 mg/kg, subcutaneously), attenuated hypothermic response to 5-HTP. These results suggest that in mice, 5-HT2A receptors are unlikely to be involved in 5-HT-mediated thermoregulation.