Premium
Chronic fluoxetine induces region‐specific changes in translation factor eIF4E and eEF2 activity in the rat brain
Author(s) -
Dagestad Grethe,
Kuipers Sjoukje D.,
Messaoudi Elhoucine,
Bramham Clive R.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.04817.x
Subject(s) - fluoxetine , dentate gyrus , antidepressant , eif4e , serotonergic , pharmacology , hippocampus , neuroscience , psychology , translation (biology) , medicine , biology , messenger rna , gene , serotonin , genetics , receptor
The delayed therapeutic onset observed in response to chronic antidepressant drug treatment is little understood. While current theories emphasize effects on gene transcription, possible effects of antidepressant drugs on translation control pathways have not been explored. We examined the effect of the selective serotonergic reuptake inhibitor fluoxetine on regulation of two major determinants of mRNA translation, eukaryotic initiation factor 4E (eIF4E) and eukaryotic elongation factor 2 (eEF2). Chronic fluoxetine treatment induced hyperphosphorylation of eEF2 (Thr56) in prefrontal cortex, hippocampus and dentate gyrus of rats. By contrast, phosphorylation of eIF4E (Ser209) was observed specifically in the dentate gyrus. Acute fluoxetine treatment had no effect on translational factor activity. These findings suggest that region‐specific regulation of translation contributes to the delayed action of antidepressant drugs such as fluoxetine.