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The role of 5-hydroxytryptamine receptor subtypes in the regulation of brain-derived neurotrophic factor gene expression

Lookup NU author(s): Dr Ahmad Khundakar

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Abstract

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.


Publication metadata

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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