Prolonged glucocorticoid treatment decreases cannabinoid CB, receptor density in the hippocampus
Prolonged glucocorticoid treatment decreases cannabinoid CB, receptor density in the hippocampus
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DOI：
10.1002/hipo.20386
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发表时间：
2008-01-01
期刊：
影响因子：
3.5
通讯作者：
Hillard, Cecilia J.
中科院分区：
文献类型：
--
作者：
Hill, Matthew N.;Carrier, Erica J.;Hillard, Cecilia J.
实验研究表明糖皮质激素和内源性大麻素系统之间存在双向的功能关系;然而，反复糖皮质激素治疗对内源性大麻素系统的影响尚未得到研究。在这项研究中，我们用皮质酮（20 mg/kg）单次给药或21天疗程治疗雄性大鼠，并测量海马大麻素CB、受体表达和内源性大麻素含量。皮质酮给药21天（而非单次）显著降低了海马大麻素CB 1受体的结合位点密度和蛋白质量，而不影响对CB 1受体激动剂[H-3] CP 55940的亲和力。关于海马内源性大麻素含量，急性皮质酮治疗导致花生四烯酸显著减少，但不影响2-花生四烯酸甘油，而重复皮质酮治疗没有改变花生四烯酸或2-花生四烯酸甘油的含量。这些数据支持大麻素CBI受体在海马中受糖皮质激素负调节的假设，并表明在与糖皮质激素分泌过多相关的条件下，如慢性应激，海马大麻素CRI受体信号传导可能减少。(c)2007 Wiley-Liss，Inc.
Experimental studies indicate a bidirectional, functional relationship between glucocorticoids and the endocannabinoid system; however, the effects of repeated glucocorticoid treatment on the endocannabinoid system have not been examined. In this study, we treated male rats with either a single dose or a 21-day course of treatment with corticosterone (20 mg/kg) and measured hippocampal cannabinoid CB, receptor expression and endocannabinoid content. The 21-day, but not the single, administration of corticosterone significantly reduced both the binding site density and amount of protein of the hippocampal cannabinoid CB, receptor without affecting affinity for the CB, receptor agonist, [H-3]CP55940. With regard to hippocampal endocannabinoid content, acute corticosterone treatment resulted in a significant reduction in anandamide but did not affect 2-arachidonylglycerol, while repeated corticosterone treatment did not alter content of either anandamide or 2-arachidonylglycerol. These data support the hypothesis that the cannabinoid CB, receptor is under negative regulation by glucocorticoids in the hippocampus, and suggest that hippocampal cannabinoid CRI receptor signaling could be reduced under conditions associated with hypersecretion of glucocorticoids, such as chronic stress. (c) 2007 Wiley-Liss, Inc.