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

Authors

  • Tyra S. C. Zetterström,

    Corresponding author
    1. Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort University, Leicester, UK
    • Correspondence

      Tyra S. C. Zetterström, Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort University, The Gateway, LE1 9BH Leicester, UK.

      E-mail: addresses: tscz@dmu.ac.uk

    Search for more papers by this author
  • Alexander A. Coppell,

    1. Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort University, Leicester, UK
    Search for more papers by this author
  • Ahmad A. Khundakar

    1. Institute for Ageing and Health, Newcastle University, Campus For Ageing and Vitality, Newcastle, UK
    Search for more papers by this author

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 down-regulation 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 fluoxetine-induced 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.

Ancillary