期刊
NEUROPHARMACOLOGY
卷 39, 期 8, 页码 1413-1421出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0028-3908(00)00052-6
关键词
NK1 receptor antagonists; anxiety; depression; NKIR -/- mice; vocalisation
The regulation of stress-induced vocalisations by central NK1 receptors was investigated using pharmacological antagonists in guinea-pigs, a species with human-like NK1 receptors, and transgenic NK1R-/- mice. In guinea-pigs, i.c.v. infusion of the selective substance P agonist GR73632 (0.1 nmol) elicited a pronounced vocalisation response that was blocked enantioselectively by the NK1 receptor antagonists CP-99,994 and L-733,060 (0.1-10 mg/kg). GR73632-induced vocalisations were also markedly attenuated by the antidepressant drugs imipramine and fluoxetine (30 mg/kg), but not by the benzodiazepine anxiolytic diazepam (3 mg/kg) or the 5-HT1A agonist buspirone (10 mg/kg). Similarly, vocalisations in guinea-pig pups separated from their mothers were blocked enantioselectively by the highly brain-penetrant NK1 receptor antagonists L-733,060 and GR205171 (ID50 3 mg/kg), but not by the poorly brain-penetrant compounds LY303870 and CGP49823 (30 mg/kg). Separation-induced vocalisations were also blocked by the anxiolytic drugs diazepam, chlordiazepoxide and buspirone (ID50 0.5-1 mg/kg), and by the antidepressant drugs phenelzine, imipramine, fluoxetine and venlafaxine (ID50 3-8 mg/kg). In normal mouse pups, GR205171 attenuated neonatal vocalisations when administered at a high dose (30 mg/kg) only, consistent with its lower affinity for the rat than the guinea-pig NK1 receptor. Ultrasound calls in NK1R-/- mouse pups were markedly reduced compared with those in WT pups, confirming the specific involvement of NK1 receptors in the regulation of vocalisation. These observations suggest that centrally-acting NK1 receptor antagonists may have clinical utility in the treatment of a range of anxiety and mood disorders. (C) 2000 Elsevier Science Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据