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

87 Citations (Scopus)

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

Fingerprint

olanzapine
Fluoxetine
Fibroblast Growth Factor 2
Brain
Treatment-Resistant Depressive Disorder
Prefrontal Cortex
Second-Generation Antidepressive Agents
Proto-Oncogene Proteins c-akt
Messenger RNA
Ribonucleases
Pharmaceutical Preparations
Antipsychotic Agents
Hippocampus
Western Blotting

Keywords

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

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Fluoxetine and olanzapine have synergistic effects in the modulation of fibroblast growth factor 2 expression within the rat brain. / Maragnoli, Maria Elisabetta; Fumagalli, Fabio; Gennarelli, Massimo; Racagni, Giorgio; Riva, Marco Andrea.

In: Biological Psychiatry, Vol. 55, No. 11, 01.06.2004, p. 1095-1102.

Research output: Contribution to journalArticle

Maragnoli, Maria Elisabetta ; Fumagalli, Fabio ; Gennarelli, Massimo ; Racagni, Giorgio ; Riva, Marco Andrea. / Fluoxetine and olanzapine have synergistic effects in the modulation of fibroblast growth factor 2 expression within the rat brain. In: Biological Psychiatry. 2004 ; Vol. 55, No. 11. pp. 1095-1102.
@article{dd92fbd621904a3fb82f770a4d8b7f75,
title = "Fluoxetine and olanzapine have synergistic effects in the modulation of fibroblast growth factor 2 expression within the rat brain",
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.",
keywords = "Akt, depression, dopamine, Neurotrophic factor, plasticity, prefrontal cortex",
author = "Maragnoli, {Maria Elisabetta} and Fabio Fumagalli and Massimo Gennarelli and Giorgio Racagni and Riva, {Marco Andrea}",
year = "2004",
month = "6",
day = "1",
doi = "10.1016/j.biopsych.2004.02.003",
language = "English",
volume = "55",
pages = "1095--1102",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "11",

}

TY - JOUR

T1 - Fluoxetine and olanzapine have synergistic effects in the modulation of fibroblast growth factor 2 expression within the rat brain

AU - Maragnoli, Maria Elisabetta

AU - Fumagalli, Fabio

AU - Gennarelli, Massimo

AU - Racagni, Giorgio

AU - Riva, Marco Andrea

PY - 2004/6/1

Y1 - 2004/6/1

N2 - 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.

AB - 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.

KW - Akt

KW - depression

KW - dopamine

KW - Neurotrophic factor

KW - plasticity

KW - prefrontal cortex

UR - http://www.scopus.com/inward/record.url?scp=2542463337&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2542463337&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2004.02.003

DO - 10.1016/j.biopsych.2004.02.003

M3 - Article

VL - 55

SP - 1095

EP - 1102

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 11

ER -