Comparative effects of serotonergic agonists with varying efficacy at the 5-HT1A receptor on core body temperature: modification by the selective 5-HT1A receptor antagonist WAY 100635

A reduction in core body temperature is one of the characteristic-consequen ces of 5-HT1A receptor activation in rodents. In this study we characterize d the hypothermic effects of four 5-HT1A receptor ligands with varying affi nity and selectivity at the 5-HT1A receptor. 8-OH-DPAT and flesinoxan (full agonists); ipsapirone (select;ive partial agonist) and eltoprazine (non se lective partial agonist), all induced a dose-dependent reduction in core bo dy temperature, which was maximal 30 min subsequent to administration. This response differed quantitatively between the agonists, in both the extent and the duration of its effects. The selective 5-HT1A receptor antagonist W AY 100635 (0.15 mg/kg), attenuated the hypothermia induced by the partial a gonists, ipsapirone (10 mg/kg)and eltoprazine (10 mg/kg). In contrast, the higher dose of WAY 100635 (1 mg/kg) antagonized the effects of all agonists ,This study therefore further confirms the utility of hypothermia as a simp le, robust in-vivo probe of 5-HT1A receptor Function. This paradigm, which was enhanced by use of specific antagonists such as WAY 100635, may prove u seful for the detection and characterization of novel 5-HT1A receptor ligan ds.