Acute and chronic effects of corticosterone on 5-HT1A receptor-mediated autoinhibition in the rat dorsal raphe nucleus
Acute and chronic effects of corticosterone on 5-HT1A receptor-mediated autoinhibition in the rat dorsal raphe nucleus
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DOI：
10.1016/s0028-3908(03)00269-7
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发表时间：
2003-12-01
影响因子：
4.7
通讯作者：
Ingram, CD
中科院分区：
文献类型：
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作者：
Fairchild, G;Leitch, MM;Ingram, CD
皮质类固醇对5-HT1a受体功能的调节可能参与了情感性精神障碍的活动。为了研究皮质酮对大鼠中缝背核(DRN)5-HT1a自身受体功能的影响，用体外电生理学方法研究了急慢性皮质酮对大鼠中缝背核(DRN)5-HT1a自身受体功能的影响。急性应用皮质酮(30-200 NM)或地塞米松(100 NM)不影响对亚最大剂量5-羟色胺的抑制反应的大小和时间进程，无论是在记录前两周的对照组大鼠脑片上还是在肾上腺切除的大鼠上。慢性治疗组大鼠饮用含皮质酮(50µg/ml)或乙醇(0.5%)的饮用水25~31天。皮质酮治疗组对5-羟色胺的自身抑制反应显著减弱，载体EC50=48+/-8um，而皮质酮EC50=121+/-20um。此外，皮质酮处理的动物的一组5-羟色胺神经元对5-羟色胺显着不敏感。原位杂交组织化学显示皮质酮不影响5-HT1a受体和G蛋白内向整流钾通道(GIRK)1型和3型亚基的表达。而GIRK2亚单位mRNA表达显著降低。因此，DRN中的5-HT1AA自身受体功能在慢性但不是急性暴露于皮质酮水平升高后减弱，这种影响可能涉及受体-效应器耦合机制的改变。(C)2003爱思唯尔有限公司。保留所有权利。
Corticosteroid modulation of 5-HT1A receptor function may contribute to the actiology of affective disorders. To examine this modulation, the effects of acute and chronic corticosterone administration on 5-HT1A autoreceptor function were investigated using in vitro electrophysiology in the rat dorsal raphe nucleus (DRN). The magnitude and time course of the inhibitory response to a submaximal dose of 5-HT was not affected by acute application of either corticosterone (30-200 nM) or dexamethasone (100 nM) in vitro, when tested either in slices from control rats or rats adrenalectomised two weeks prior to recording. For chronic treatment, rats were supplied with drinking water containing corticosterone (50 mug/ml) or ethanol vehicle (0.5%) for 25-31 days. The auto-inhibitory response to 5-HT was significantly attenuated in the corticosterone-treated group; vehicle EC50 = 48 +/- 8 muM vs. corticosterone EC50 = 121 +/- 20 muM. Furthermore a subpopulation of 5-HT neurones from corticosterone-treated animals exhibited marked insensitivity to 5-HT. In situ hybridisation histochemistry showed that corticosterone did not affect the expression of mRNA encoding the 5-HT1A receptor or either the type 1 and type 3 subunits of the G-protein linked inwardly rectifying K+ (GIRK) channel. However, GIRK2 subunit mRNA expression was significantly reduced. Thus, 5-HT1A A autoreceptor function in the DRN is attenuated following chronic, but not acute, exposure to elevated corticosterone levels, and this effect may involve changes to the receptor-effector coupling mechanism. (C) 2003 Elsevier Ltd. All rights reserved.