Psychopharmacology

, Volume 216, Issue 1, pp 75–84

Fluoxetine regulates the expression of neurotrophic/growth factors and glucose metabolism in astrocytes

  • Igor Allaman
  • Hubert Fiumelli
  • Pierre J. Magistretti
  • Jean-Luc Martin
Original Investigation

DOI: 10.1007/s00213-011-2190-y

Cite this article as:
Allaman, I., Fiumelli, H., Magistretti, P.J. et al. Psychopharmacology (2011) 216: 75. doi:10.1007/s00213-011-2190-y

Abstract

Rationale

The pharmacological actions of most antidepressants are ascribed to the modulation of serotonergic and/or noradrenergic transmission in the brain. During therapeutic treatment for major depression, fluoxetine, one of the most commonly prescribed selective serotonin reuptake inhibitor (SSRI) antidepressants, accumulates in the brain, suggesting that fluoxetine may interact with additional targets. In this context, there is increasing evidence that astrocytes are involved in the pathophysiology of major depression.

Objectives

The aim of this study was to examine the effects of fluoxetine on the expression of neurotrophic/growth factors that have antidepressant properties and on glucose metabolism in cultured cortical astrocytes.

Results

Treatment of astrocytes with fluoxetine and paroxetine, another SSRI antidepressant, upregulated brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and VGF mRNA expression. In contrast, the tricyclic antidepressants desipramine and imipramine did not affect the expression of these neurotrophic/growth factors. Analysis of the effects of fluoxetine on glucose metabolism revealed that fluoxetine reduces glycogen levels and increases glucose utilization and lactate release by astrocytes. Similar data were obtained with paroxetine, whereas imipramine and desipramine did not regulate glucose metabolism in this glial cell population. Our results also indicate that the effects of fluoxetine and paroxetine on glucose utilization, lactate release, and expression of BDNF, VEGF, and VGF are not mediated by serotonin-dependent mechanisms.

Conclusions

These data suggest that, by increasing the expression of specific astrocyte-derived neurotrophic factors and lactate release from astrocytes, fluoxetine may contribute to normalize the trophic and metabolic support to neurons in major depression.

Keywords

AntidepressantsGrowth factorsGliaSerotoninLactateGlycogen

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Igor Allaman
    • 1
  • Hubert Fiumelli
    • 2
  • Pierre J. Magistretti
    • 1
    • 3
  • Jean-Luc Martin
    • 2
    • 3
  1. 1.Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind InstituteEcole Polytechnique Fédérale de Lausanne (EPFL)LausanneSwitzerland
  2. 2.Department of PhysiologyUniversity of LausanneLausanneSwitzerland
  3. 3.Department of Psychiatry-CHUVCenter for Psychiatric NeurosciencePrilly-LausanneSwitzerland