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

被引:61
作者
Cryan, JF
Kelliher, P
Kelly, JP
Leonard, BE
机构
[1] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA
[2] Natl Univ Ireland Univ Coll Galway, Dept Pharmacol, Galway, Ireland
关键词
5-HT1A agonists; hypothermia; 5-HT1A receptor; WAY; 100635;
D O I
10.1177/026988119901300310
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 (select;ive 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-HT1A receptor 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 (1 mg/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-HT1A receptor ligands.
引用
收藏
页码:278 / 283
页数:6
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