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Basic Fibroblast Growth Factor Prevents the Memory Impairment Induced by Gastrin-Releasing Peptide Receptor Antagonism in Area CA1 of the Rat Hippocampus

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Abstract

Increasing evidence indicates that the gastrin-releasing peptide receptor (GRPR) is implicated in regulating synaptic plasticity and memory formation in the hippocampus and other brain areas. However, the molecular mechanisms underlying the memory-impairing effects of GRPR antagonism have remained unclear. Here we report that basic fibroblast growth factor (bFGF/FGF-2) rescues the memory impairment induced by GRPR antagonism in the rat dorsal hippocampus. The GRPR antagonist [D-Tpi6, Leu13 psi(CH2NH)-Leu14] bombesin (6–14) (RC-3095) at 1.0 μg impaired, whereas bFGF at 0.25 μg enhanced, 24 h retention of inhibitory avoidance (IA) when infused immediately after training into the CA1 hippocampal area in male rats. Coinfusion with an otherwise ineffective dose of bFGF blocked the memory-impairing effect of RC-3095. These findings suggest that the memory-impairing effects of GRPR antagonists might be partially mediated by an inhibition in the function and/or expression of neuronal bFGF or diminished activation of intracellular protein kinase pathways associated with bFGF signaling.

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Acknowledgments

This research was supported by CNPq Grants 306413/2003-5 and 474700/2004-6 to R.R. and the South American Office for Anticancer Drug Development. RC-3095 was a gift from Zentaris GmbH (Frankfurt, Germany).

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Authors and Affiliations

  1. Department of Pharmacology, Institute for Basic Health Sciences, Cellular and Molecular Neuropharmacology Research Group, Federal University of Rio Grande do Sul, 90046-900, Porto Alegre, RS, Brazil

    Thales Preissler & Rafael Roesler

  2. Department of Biochemistry, Institute for Basic Health Sciences, Graduate Program in Biochemistry, Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil

    Tatiana Luft

  3. Bipolar Disorders Program, Academic Hospital Research Center, Faculty of Medicine, Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil

    Flávio Kapczinski

  4. Department of Medicine, Laboratory of Neurosciences, University of Southern Santa Catarina, 88806-000, Criciuma, SC, Brazil

    João Quevedo

  5. Department of Internal Medicine, Faculty of Medicine, Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil

    Gilberto Schwartsmann

  6. Cancer Research Laboratory, Academic Hospital Research Center, Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil

    Gilberto Schwartsmann & Rafael Roesler

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  1. Thales Preissler
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Correspondence to Rafael Roesler.

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Preissler, T., Luft, T., Kapczinski, F. et al. Basic Fibroblast Growth Factor Prevents the Memory Impairment Induced by Gastrin-Releasing Peptide Receptor Antagonism in Area CA1 of the Rat Hippocampus. Neurochem Res 32, 1381–1386 (2007). https://doi.org/10.1007/s11064-007-9320-2

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  • DOI: https://doi.org/10.1007/s11064-007-9320-2

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