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BDNF Level in the Rat Prefrontal Cortex Increases Following Chronic but Not Acute Treatment with Duloxetine, a Dual Acting Inhibitor of Noradrenaline and Serotonin Re-uptake

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Abstract

Aims

Brain-Derived Neurotrophic Factor (BDNF) has a central role in neuronal survival, differentiation, and plasticity. The brain level of BDNF is changed by several mood stabilizers and antidepressant drugs acting on neurotransmitters such as noradrenaline and serotonin. We investigated the effects of acute and chronic treatment with Duloxetine, a new drug blocking the re-uptake of serotonin and noradrenaline (SNRI), on BDNF level in the prefrontal cortex, cerebrospinal fluid, plasma, and serum.

Methods

Wistar male rats were treated with acute (single treatment) and chronic oral administration (14 days) of different concentrations of Duloxetine (10, 30, and 100 mg/kg/day). At the end of the treatment periods, samples of blood, CSF and the prefrontal cortex were collected. BDNF levels were measured by ELISA. Levels of mature and precursor form of BDNF were measured by Western blot analysis.

Results

Animals treated with the Duloxetine at all concentrations and examined after 1 and 24 h (single treatment) did not reveal a significant change in the total BDNF level. In animals treated for 14 days with Duloxetine at 30 and 100 mg/kg, the total BDNF level increased significantly in the prefrontal cortex and CSF, but not in the plasma and serum. Using a specific antibody and Western blot we showed that the mature, but not the precursor, form of BDNF was significantly increased in the prefrontal cortex of rats treated for 14 days with Duloxetine at 30 mg/kg/day.

Conclusions

Our results show a major finding that repeated, but not single, Duloxetine treatment increases the level of BDNF in the prefrontal cortex.

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Acknowledgments

We thank Mr. Gary Scialdone for revising the manuscript. This work was supported by Eli Lilly, Italy.

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Authors and Affiliations

  1. Department of Neuroscience, Sect. Pharmacology, University of Pisa, Pisa, Italy

    Claudio Mannari, Alessia Scatena & Luca Giovannini

  2. Institute of Neuroscience (C.N.R.), Via G. Moruzzi 1, Pisa, 56100, Italy

    Nicola Origlia & Luciano Domenici

  3. Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy

    Alessandro Del Debbio, Mario Catena, Liliana Dell’Osso & Armando Piccinni

  4. Eli Lilly Italia SpA, Firenze, Italy

    Grazia Dell’Agnello & Alessandra Barraco

  5. International School for Advanced Studies (SISSA), Trieste, Italy

    Luciano Domenici

  6. Department STB, University of L’Aquila, L’Aquila, Italy

    Luciano Domenici

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  1. Claudio Mannari
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  2. Nicola Origlia
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Correspondence to Luciano Domenici.

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Claudio Mannari and Nicola Origlia are contributed equally to this work.

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Mannari, C., Origlia, N., Scatena, A. et al. BDNF Level in the Rat Prefrontal Cortex Increases Following Chronic but Not Acute Treatment with Duloxetine, a Dual Acting Inhibitor of Noradrenaline and Serotonin Re-uptake. Cell Mol Neurobiol 28, 457–468 (2008). https://doi.org/10.1007/s10571-007-9254-x

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