title: The role of 5-hydroxytryptamine receptor subtypes in the regulation of brain-derived neurotrophic factor gene expression.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
authors.affiliation: Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort University, Leicester, UK.
authors.forename: Tyra S C
authors.initials: TS
authors.lastname: Zetterström
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Coppell
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Khundakar
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D005938:Glucocorticoids / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005473:Fluoxetine; D005938:Glucocorticoids; D009638:Norepinephrine; D011985:Receptors, Serotonin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
keywords: 5-HT receptors; antidepressant drugs; brain-derived neurotrophic factor; fluoxetine; hippocampus