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Acute and chronic effects of corticosterone on 5-HT1A receptor-mediated autoinhibition in the rat dorsal raphe nucleus

Lookup NU author(s): Graeme Fairchild, Mel LeitchORCiD, Professor Colin Ingram

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Abstract

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.

Publication metadata

Author(s): Fairchild G, Leitch MM, Ingram CD

Publication type: Article

Publication status: Published

Journal: Neuropharmacology

Year: 2003

Volume: 45

Issue: 7

Pages: 925-934

Print publication date: 01/12/2003

ISSN (print): 0028-3908

ISSN (electronic): 1873-7064

Publisher: Pergamon

URL: http://dx.doi.org/10.1016/S0028-3908(03)00269-7

DOI: 10.1016/S0028-3908(03)00269-7

PubMed id: 14573385

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