Fluoxetine and olanzapine have synergistic effects in the modulation of fibroblast growth factor 2 expression within the rat brain

Maria Elisabetta Maragnoli, Fabio Fumagalli, Massimo Gennarelli, Giorgio Racagni, Marco Andrea Riva

Research output: Contribution to journalArticle

Abstract

Background The combination of the antidepressant fluoxetine (FLX) and the atypical antipsychotic olanzapine (OLA) appears to be more effective for the treatment of resistant depression than single drugs. We hypothesize that such combination may determine a specific modulation of neuroplastic genes, which could contribute to therapeutic activity. Methods We investigated the expression of the neurotrophic molecule basic fibroblast growth factor 2 (FGF-2) after acute or chronic administration of FLX and OLA, alone or in combination. Ribonuclease (RNase) protection assay and Western blot analysis were employed to determine FGF-2 expression in different brain structures and to identify the intracellular pathways possibly involved in FGF-2 modulation. Results After single injection, we found that FGF-2 mRNA levels were selectively upregulated in the prefrontal cortex only when the two drugs were coadministered, an effect paralleled by a significant increase of phosphorylated protein kinase B (P-Akt) levels. Conversely, chronic treatment with a combination of FLX and OLA (FLX+OLA) increased FGF-2 mRNA levels in prefrontal cortex, as well as in hippocampus and striatum. Conclusions Based on these data, we hypothesize a role of endogenously synthesized FGF-2 in the effects of FLX/OLA combination on brain function and plasticity, which could contribute to its superior efficacy for the treatment of resistant depression.

Original languageEnglish
Pages (from-to)1095-1102
Number of pages8
JournalBiological Psychiatry
Volume55
Issue number11
DOIs
Publication statusPublished - Jun 1 2004

Keywords

  • Akt
  • depression
  • dopamine
  • Neurotrophic factor
  • plasticity
  • prefrontal cortex

ASJC Scopus subject areas

  • Biological Psychiatry

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