The anxiolytic effect of the CRH1 receptor antagonist R121919 depends on innate emotionality in rats

被引：134

作者：

Keck, ME ^{[1
]}

Welt, T ^{[1
]}

Wigger, A ^{[1
]}

Renner, U ^{[1
]}

Engelmann, M ^{[1
]}

Holsboer, F ^{[1
]}

Landgraf, R ^{[1
]}

机构：

[1] Max Planck Inst Psychiat, D-80804 Munich, Germany

来源：

EUROPEAN JOURNAL OF NEUROSCIENCE | 2001年 / 13卷 / 02期

关键词：

anxiety; corticotropin-releasing factor; corticotropin-releasing hormone receptor antagonist; corticotropin-releasing hormone; depression; stress;

D O I：

10.1046/j.0953-816X.2000.01383.x

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Hyperactivity of central corticotropin-releasing hormone (CRH) circuits appears to contribute to the symptomatology of affective and anxiety disorders and therefore CRH receptor antagonists have attracted attention as potential therapeutic agents. R121919, a novel high-affinity nonpeptide CRH1 receptor antagonist, displaced I-125-oCRH in rat pituitary, cortex and amygdala, but not in choroid plexus or cerebral blood vessels in vitro and in vivo, which is consistent with CRH1 receptor antagonism. In vivo, R121919 significantly inhibited stress-induced corticotropin release in rats selectively bred for high- and low-anxiety-related behaviour but displayed anxiolytic effects in high-anxiety rats only. These data, corroborated by ex vivo receptor occupancy studies, suggest that this animal model is appropriate for the evaluation of CRH1 receptor antagonists and that compounds such as R121919 will be beneficial whenever the central stress hormone system is hyperactive.

引用

页码：373 / 380

页数：8

共 45 条

[1] CRF AND RESTRAINT-STRESS DECREASE EXPLORATORY-BEHAVIOR IN HYPOPHYSECTOMIZED MICE [J].