Synergism between fluoxetine and the mGlu2/3 receptor agonist, LY379268, in an in vitro model for antidepressant drug-induced neurogenesis

Francesco Matrisciano*, M. Zusso, I. Panaccione, B. Turriziani, A. Caruso, L. Iacovelli, L. Noviello, G. Togna, D. Melchiorri, P. Debetto, R. Tatarelli, G. Battaglia, F. Nicoletti, P. Giusti, P. Girardi

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

We examined the interaction between the selective serotonin reuptake inhibitor, fluoxetine, and group-II metabotropic glutamate (mGlu) receptors using progenitor cells isolated from cultured cerebellar granule cells, considered as an in vitro model of antidepressant-drug induced neurogenesis. These cells expressed mGlu3 receptors negatively coupled to adenylyl cyclase. A 72-h treatment with either fluoxetine or low concentrations of mGlu2/3 receptor agonists (LY379268 or 2R,4R-APDC) enhanced cell proliferation. The action of fluoxetine was mediated by the activation of 5-HT1A receptors. We found a strong synergism between fluoxetine and LY379268 in enhancing cell proliferation and inhibiting cAMP formation. The increased cell proliferation induced by fluoxetine + LY379268 was abrogated by the cAMP analogue, 8-Br-cAMP, as well as by drugs that inhibit the mitogen-activated protein kinase and phosphatidyilinositol-3-kinase pathways. Interestingly, fluoxetine and LY379268 also acted synergistically in promoting neuronal differentiation when progenitor cells were incubated in the presence of serum. These data support the hypothesis that a combination between classical antidepressants and mGlu2/3 receptor agonists may be helpful in the experimental treatment of depression.

Original languageEnglish (US)
Pages (from-to)428-437
Number of pages10
JournalNeuropharmacology
Volume54
Issue number2
DOIs
StatePublished - Feb 1 2008

Keywords

  • Cell proliferation
  • Cerebellar progenitors
  • Fluoxetine
  • Neurogenesis
  • mGlu3 receptors

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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    Matrisciano, F., Zusso, M., Panaccione, I., Turriziani, B., Caruso, A., Iacovelli, L., Noviello, L., Togna, G., Melchiorri, D., Debetto, P., Tatarelli, R., Battaglia, G., Nicoletti, F., Giusti, P., & Girardi, P. (2008). Synergism between fluoxetine and the mGlu2/3 receptor agonist, LY379268, in an in vitro model for antidepressant drug-induced neurogenesis. Neuropharmacology, 54(2), 428-437. https://doi.org/10.1016/j.neuropharm.2007.10.020