Anxiolytic properties of the selective, non-peptidergic CRF1 antagonists, CP154,526 and DMP695:: A comparison to other classes of anxiolytic agent

被引:91
作者
Millan, MJ
Brocco, M
Gobert, A
Dorey, G
Casara, P
Dekeyne, A
机构
[1] Ctr Rech Croissy, Inst Rech Servier, Chem Dept A, Paris, France
[2] Ctr Rech Croissy, Inst Rech Servier, Dept Psychopharmacol, Paris, France
关键词
CRF1; receptors; 5-HT1A receptors; 5-HT2C receptors; benzodiazepines; anxiety;
D O I
10.1016/S0893-133X(01)00244-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The selective, non-peptidergic corticotropin-releasing factor (CRF), receptor antagonists, CP154,526 and DMP695, dose-dependently increased punished responses Of rats in a Vogel conflict test and enhanced social interaction (SI) of rats in an unfamiliar environment. They were, however, inactive in a plus-maze procedure and failed to reduce ultrasonic vocalizations (USV) associated with an aversive environment. In contrast, the benzodiazopine, chlordiazepoxide, was effective in all these procedures. Further, the serotonin (5-HT)(1A) agonist, flesinoxan, was active in each paradigm (except the plus-maze) while the 5-HT2C antagonist, SB242,084, was effective in the S1 and Vogel but not the plus-maze and USV procedures. In contrast to chlordiazepoxide, flesinoxan and SB242,084, CP154,526 did not modify dialysate levels of 5-HT, norepinephrine (NE) and dopamine (DA) in the frontal cortex (FCX) of freely moving rats. In conclusion, CP154,526 and DMP695 possess a common and distinctive profile of anxiolytic action expressed in the absence of an intrinsic influence upon monoamine release.
引用
收藏
页码:585 / 600
页数:16
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