Acute and chronic effects of corticosterone on 5-HT1A receptor-mediated autoinhibition in the rat dorsal raphe nucleus.
Corticosteroid modulation of 5-HT(1A) 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 microg/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 microM vs. corticosterone EC(50)=121+/-20 microM. 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-HT(1A) 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-HT(1A) 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.
Psychobiology Research Group, School of Neurology, Neurobiology and Psychiatry, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK.
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000315:Adrenalectomy; D000818:Animals; D001345:Autoradiography; D002940:Circadian Rhythm; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger / Q000096:biosynthesis; D011903:Raphe Nuclei / Q000187:drug effects*; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone