期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 624, 期 1-3, 页码 71-76出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2009.09.055
关键词
Cannabinoid; CB1 receptor; Serotonin; Raphe; Norepinephrine; Locus coeruleus; Glutamate
资金
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Canadian Institutes of Health Research (CIHR)
- Michael Smith Foundation for Health Research (MSFHR)
Administration of high doses of cannabinoid CB1 receptor agonists activates the hypothalamic-pituitaty-adrenal (HPA) axis; however, the mechanism by which this occurs has not been well characterized. Both monoaminergic and glutamatergic neurotrans mission are known to activate the HPA axis and cannabinoids have been found to modify levels of these neurotransmitters. Employing pharmacological antagonists to specific serotonergic, noradrenergic and glutamatergic receptor subtypes, we examined whether activation of these receptors is involved in the ability of a high dose of a cannabinoid CB1 receptor agonist to activate the HPA axis. We characterized a robust induction of corticosterone secretion following administration of a 100 mu g/kg dose of HU-210, a potent cannabinoid CB1 receptor agonist. Pre-treatment with antagonists to the serotonergic type 1A (5-HT1A; WAY100635: 0.5 mg/kg) and 5-HT2A/2c (ketanserin; 1 mg/kg) receptors significantly attenuated the HU-210-induced increase in corticosterone secretion. Similarly, the increase in corticosterone secretion following HU-210 administration was significantly reduced by pre-treatment with antagonists to the alpha(1)-adrenoceptor (prazosin; 1 mg/kg) and beta-adrenoceptor (propanolol; 2.5 mg/kg). However, pre-treatment with antagonists to the NMDA (MK-801; 0.1 mg/kg) and AMPA/Kainate (DNQX; 10 mg/kg) receptors did not modify activation of adrenocortical secretion evoked by HU-210. These data suggest that acute administration of exogenous cannabinoid ligands activates the HPA axis indirectly through an increase in serotonergic and noradrenergic neurotransmission. (C) 2009 Elsevier B.V. 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