Basal and stress-induced modulation of activity-regulated cytoskeletal associated protein (Arc) in the rat brain following duloxetine treatment.
BACKGROUND
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.
Molteni
Raffaella
R
Center of Neuropharmacology, Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy.
Calabrese
Francesca
F
Mancini
Michele
M
Racagni
Giorgio
G
Riva
Marco A
MA
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000068736:Duloxetine Hydrochloride; D018728:Entorhinal Cortex / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D009044:Motor Cortex / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005082:Physical Exertion; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000188:drug therapy* / Q000209:etiology*; D013550:Swimming; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D015854:Up-Regulation
D000928:Antidepressive Agents; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D013876:Thiophenes; C092069:activity regulated cytoskeletal-associated protein; D000068736:Duloxetine Hydrochloride