Chronic fluoxetine induces region-specific changes in translation factor eIF4E and eEF2 activity in the rat brain.
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.
Dagestad
Grethe
G
Department of Biomedicine, University of Bergen, and Bergen Mental Health Research Center, Jonas Lies vei 91, N-5009 Bergen, Norway.
Kuipers
Sjoukje D
SD
Messaoudi
Elhoucine
E
Bramham
Clive R
CR
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004334:Drug Administration Schedule; D004591:Electrophoresis, Polyacrylamide Gel; D039561:Eukaryotic Initiation Factor-4E / Q000187:drug effects* / Q000378:metabolism; D005473:Fluoxetine / Q000008:administration & dosage*; D007150:Immunohistochemistry; D008297:Male; D020652:Peptide Elongation Factor 2 / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*
D039561:Eukaryotic Initiation Factor-4E; D005473:Fluoxetine; D020652:Peptide Elongation Factor 2; D017367:Selective Serotonin Reuptake Inhibitors