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Lookup NU author(s): Dr Ahmad Khundakar
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Objectives The study aims to investigate the role of 5-hydroxytryptamine receptor subtypes in mediating the inhibitory effect of the selective serotonin reuptake inhibitor (fluoxetine on brain-derived neurotrophic factor gene (bdnf) expression in rat hippocampus. Methods In situ hybridization was used for regional determination of bdnf expression levels in hippocampal brain slices from normal, lesioned (5-hydroxytryptamine or noradrenaline) or adrenalectomized rats; treated with fluoxetine and/or 5-hydroxytryptamine selective ligands. Key findings Our study shows that the transient fluoxetine-induced downregulation of bdnf gene expression depends on an intact 5-hydroxytryptamine but not noradrenaline system or circulating glucocorticoids. Pretreatment with the 5-hydroxytryptamine4 antagonist SB-204070 blocked the overall fluoxetineinduced inhibition of bdnf levels in hippocampus, while pretreatment with the 5-hydroxytryptamine2 antagonists ketanserin had an effect in the CA3 but not in the dentate gyrus sub-region of hippocampus. The 5-hydroxytryptamine1A antagonist WAY-100635 and the 5-hydroxytryptamine3 antagonist granisetron were both ineffective. Conclusions Our study found strong support for a primary effect of 5-hydroxytryptamine but not noradrenaline or circulating glucocorticoids in the mediation of fluoxetine-induced down-regulation of bdnf expression. More specifically, we also show that 5-hydroxytryptamine4 receptor-stimulation seems to play a pivotal role in this effect.
Author(s): Zetterström TSC, Coppell AA, Khundakar AA
Publication type: Article
Publication status: Published
Journal: Journal of Pharmacy and Pharmacology
Year: 2014
Volume: 66
Issue: 1
Pages: 53-61
Print publication date: 01/01/2014
Online publication date: 07/10/2013
Acceptance date: 05/09/2013
ISSN (print): 0022-3573
ISSN (electronic): 2042-7158
Publisher: Royal Pharmaceutical Society
URL: http://dx.doi.org/10.1111/jphp.12153
DOI: 10.1111/jphp.12153
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