Abstract
Compelling evidence suggests that mood disorders are characterized by reduced neuronal plasticity that might be normalized by pharmacological intervention. Our study aimed to establish whether chronic antidepressant treatment could alter the modulation of the neurotrophin brain-derived neurotrophic factor (BDNF) under a stressful condition. Therefore, adult male Sprague–Dawley rats were treated for 21 days with vehicle or with the SNRI duloxetine and, 24 h after the last injection, exposed to an acute swim stress (5 min) before being killed 15 min later. We found that chronic duloxetine treatment was able to modulate the rapid transcriptional changes of BDNF isoforms produced by an acute swim stress. Indeed whereas the mRNA levels of BDNF exon IV were upregulated by stress in vehicle as well as in duloxetine-treated rats, a significant increase of exon VI and exon IX was only found in rats that were pretreated with the antidepressant. These differential effects are in part because of selective changes in signaling pathways involved in the control of BDNF transcription. Moreover, the acute stressful episode significantly increased the levels of mature BDNF protein in the synaptosomal compartment in rats that were pretreated with the antidepressant, but not in control animals. Our results suggest that chronic antidepressant treatment might affect the responsiveness of BDNF under stressful conditions, suggesting that pharmacological intervention could ‘prime’ neuroprotective pathways and render them more responsive to preserve cell function and viability.
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Acknowledgements
Special thanks to Dr J Richetto for contributing to part of this study and to Professor ME Greenberg for the generous gift of MeCP2 antibodies. This research has been supported by funding to MAR from the Italian Ministry of University and Research (PRIN2005 n. 2005059982), the Ministry of Health, and by an unrestricted grant from Eli Lilly Italia SpA.
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All authors have no financial interests or potential conflicts of interest to declare. Dr Michele Mancini is an employee of Eli Lilly Italia holding Eli Lilly nonqualified stock option shares.
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Molteni, R., Calabrese, F., Cattaneo, A. et al. Acute Stress Responsiveness of the Neurotrophin BDNF in the Rat Hippocampus is Modulated by Chronic Treatment with the Antidepressant Duloxetine. Neuropsychopharmacol 34, 1523–1532 (2009). https://doi.org/10.1038/npp.2008.208
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DOI: https://doi.org/10.1038/npp.2008.208
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