5-HTT independent effects of fluoxetine on neuroplasticity

Marion J. F. Levy, Fabien Boulle, Michel Boris Emerit, Corinne Poilbout, Harry W. M. Steinbusch, Daniel L. A. Van den Hove, Gunter Kenis, Laurence Lanfumey*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

20 Citations (Web of Science)

Abstract

Selective serotonin reuptake inhibitors are among the most prescribed antidepressants. Fluoxetine is the lead molecule which exerts its therapeutic effects, at least in part, by promoting neuroplasticity through increased brain-derived neurotrophic factor (BDNF)/tropomyosin-related receptor kinase B (TrkB) signalling. It is unclear however, to which extent the neuroplastic effects of fluoxetine are solely mediated by the inhibition of the serotonin transporter (5-HTT). To answer this question, the effects of fluoxetine on neuroplasticity were analysed in both wild type (WT) and 5-Htt knock-out (KO) mice. Using Western blotting and RT-qPCR approaches, we showed that fluoxetine 10 mu M activated BDNF/TrkB signalling pathways in both CD1 and C57BL/6J mouse primary cortical neurons. Interestingly, effects on BDNF signalling were observed in primary cortical neurons from both 5-Htt WT and KO mice. In addition, a 3-week in vivo fluoxetine treatment (15 mg/kg/d; i.p.) increased the expression of plasticity genes in brains of both 5-Htt WT and KO mice, and tended to equally enhance hippocampal cell proliferation in both genotypes, without reaching significance. Our results further suggest that fluoxetine-induced neuroplasticity does not solely depend on 5-HTT blockade, but might rely, at least in part, on 5-HTT-independent direct activation of TrkB.

Original languageEnglish
Article number6311
Number of pages11
JournalScientific Reports
Volume9
DOIs
Publication statusPublished - 19 Apr 2019

Keywords

  • TYROSINE KINASE-B
  • NEUROTROPHIC FACTOR
  • ANTIDEPRESSANT DRUGS
  • SYNAPTIC PLASTICITY
  • POSTMORTEM BRAIN
  • GENE-EXPRESSION
  • MESSENGER-RNA
  • MOUSE MODEL
  • RECEPTOR
  • ACTIVATION

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