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Lookup NU author(s): Graeme Fairchild,
Professor Colin Ingram
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Corticosteroid modulation of 5-HT1A receptor function may contribute to the aetiology of affective disorders. To examine this modulation, the effects of acute and chronic corticosterone administration on 5-HT 1A 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 μg/ml) or ethanol vehicle (0.5%) for 25-31 days. The autoinhibitory response to 5-HT was significantly attenuated in the corticosterone-treated group; vehicle EC 50=48±8 μM vs. corticosterone EC50= 121±20 μM. 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 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. © 2003 Elsevier Ltd. All rights reserved.
Author(s): Fairchild G, Leitch MM, Ingram CD
Publication type: Article
Publication status: Published
Print publication date: 01/12/2003
ISSN (print): 0028-3908
ISSN (electronic): 1873-7064
PubMed id: 14573385
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