EVIDENCE FOR FUNCTIONAL INTERACTIONS BETWEEN 5-HT1A AND 5-HT2A RECEPTORS IN RAT THERMOREGULATORY MECHANISMS

The present study was designed to examine 1) functional interactions b etween 5-HT1A and 5-HT2A/C receptors in thermoregulation in rats and 2 ) the specific involvement of 5-HT2A and 5-HT2C receptors in such inte ractions. The 5-HT2A/C receptor agonist DOI (0.025-1.6 mg kg(-1), subc utaneously) produced a dose-dependent hyperthermia in rats, which was enhanced by addition of either of two 5-HT1A receptor antagonists, (-) -pindolol (0.5-1.0 mg kg(-1), subcutaneously) or WAY-100,635 (0.1-0.4 mg kg(-1), subcutaneously). Furthermore, the DOI-induced hyperthermia was counteracted by pretreatment with the 5-HT1A receptor agonist 8-OH -DPAT (0.05 mg kg(-1), subcutaneously). The hyperthermia produced by D OI, alone or in combination with WAY-100,635, was fully antagonized by pretreatment with the 5-HT2A/C receptor antagonist ritanserin (1.0 mg kg(-1), subcutaneously), as well as with the selective 5-HT2A recepto r antagonist amperozide (2.0 mg kg(-1), subcutaneously). The present r esults provide evidence for functional interactions between 5-HT1A and 5-HT2A receptors in temperature regulation in rats, and also suggest an important role for postsynaptic 5-HT2A receptors in the mediation o f DOI-induced hyperthermia.