Abstract
Rationale
Therapeutic efficacy of antidepressant drugs appears to be related to their ability in producing neuroadaptive changes that restore normal brain function. Activity-regulated cytoskeletal associated protein (Arc) is an effector immediate early gene that plays a fundamental role in activity-dependent neural plasticity in corticolimbic brain regions and has been implicated in the modulation of several functions known to be profoundly perturbed in depressive states.
Objective
In the present study, we investigated transcriptional and translational changes of Arc in response to acute or chronic treatment with the novel antidepressant duloxetine.
Results
Although a limited increase of Arc messenger RNA (mRNA) levels was found in some structures after acute antidepressant administration, a marked up-regulation of its gene expression was found after chronic treatment, primarily at the level of frontal cortex. The changes observed after prolonged duloxetine administration strongly correlates with those previously reported on brain-derived neurotrophic factor mRNA levels Calabrese et al. (Neuropsychopharmacol 32:2351–2359, 2007). In addition, we found an anatomical-specific influence of chronic duloxetine on stress-dependent Arc modulation, which was limited to the frontal cortex.
Conclusions
We suggest that these neuroadaptive changes, among others, might contribute to the normalization of neuroplastic defects associated with mood disorders.
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Acknowledgements
Special thanks to Dr. P.F. Maj and F. Bolis for contributing to a part of this study. This research has been supported by funding to M.A.R. from the Italian Ministry of University (PRIN n.2005059982) and Research, the Ministry of Health, and by an unrestricted grant from Eli Lilly Italia S.p.A.
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Molteni, R., Calabrese, F., Mancini, M. et al. Basal and stress-induced modulation of activity-regulated cytoskeletal associated protein (Arc) in the rat brain following duloxetine treatment. Psychopharmacology 201, 285–292 (2008). https://doi.org/10.1007/s00213-008-1276-7
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DOI: https://doi.org/10.1007/s00213-008-1276-7