Basal and stress-induced modulation of activity-regulated cytoskeletal associated protein (Arc) in the rat brain following duloxetine treatment.

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.

journal_title

Psychopharmacology

authors

Molteni R,Calabrese F,Mancini M,Racagni G,Riva MA

doi

10.1007/s00213-008-1276-7

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

285-92

issue

2

eissn

0033-3158

issn

1432-2072

journal_volume

201

pub_type

杂志文章
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