Chronic fluoxetine induces region-specific changes in translation factor eIF4E and eEF2 activity in the rat brain

doi:10.1111/j.1460-9568.2006.04817.x

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Wiley InterScience

European Journal of Neuroscience

Volume 23 Issue 10, Pages 2814 - 2818

Published Online: 31 May 2006

Published on behalf of the Federation of European Neuroscience Societies

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SHORT COMMUNICATION

Chronic fluoxetine induces region-specific changes in translation factor eIF4E and eEF2 activity in the rat brain

Grethe Dagestad, Sjoukje D. Kuipers, Elhoucine Messaoudi and Clive R. Bramham

Department of Biomedicine, University of Bergen, and Bergen Mental Health Research Center, Jonas Lies vei 91, N-5009 Bergen, Norway

Correspondence to Dr C. Bramham, as above.
E-mail: clive.bramham@biomed.uib.no

Copyright The Authors (2006). Journal Compilation Federation of European Neuroscience Societies and Blackwell Publishing Ltd

KEYWORDS

antidepressant • brain-derived neurotrophic factor • hippocampus • protein synthesis • synaptic plasticity • translation control

ABSTRACT

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.

Received 1 September 2005, revised 14 February 2006, accepted 13 March 2006

DIGITAL OBJECT IDENTIFIER (DOI)

10.1111/j.1460-9568.2006.04817.x About DOI

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