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

F. 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

Research output: Contribution to journalArticle

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
Pages (from-to)428-437
Number of pages10
JournalNeuropharmacology
Volume54
Issue number2
DOIs
Publication statusPublished - Feb 2008

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

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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