Affiliation:
1. Department of Pharmacology 320 Morgan Building (6084) 3620 Hamilton Walk University of Pennsylvania Philadelphia, PA 19104 USA
2. Department of Pharmacology, National University of Ireland, Galway, Ireland
Abstract
A reduction in core body temperature is one of the characteristic consequences of 5-HT1A receptor activation in rodents. In this study, we characterized the hypothermic effects of four 5-HT1A receptor ligands with varying affinity and selectivity at the 5-HT1A receptor. 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-HT1A receptor 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.
Subject
Pharmacology (medical),Psychiatry and Mental health,Pharmacology
Cited by
63 articles.
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