Comparative effects of serotonergic agonists withvarying efficacy at the 5-HT1Areceptor on core body temperature: modification by the selective 5-HT1Areceptor antagonist WAY 100635

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Abstract
A reduction in core body temperature is one of the characteristic consequences of 5-HT1Areceptor activation in rodents. In this study, we characterized the hypothermic effects of four 5-HT1Areceptor ligands with varying affinity and selectivity at the 5-HT1Areceptor. 8-OH-DPAT and flesinoxan (full agonists); ipsapirone (selective partial agonist) and eltoprazine (non selective partial agonist), all induced a dose-dependent reduction in core body 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-HT1Areceptor antagonist WAY 100635 (0.15 mg/kg), attenuated the hypothermia induced by the partial agonists, ipsapirone (10 mg/kg) and eltoprazine (10 mg/kg). In contrast, the higher dose of WAY 100635 (1mg/kg) antagonized the effects of all agonists. This study therefore further confirms the utility of hypothermia as a simple, robust in-vivo probe of 5-HT1Areceptor function.This paradigm, which was enhanced by use of specific antagonists such as WAY 100635, may prove useful for the detection and characterization of novel 5-HT1Areceptor ligands.