Effects of venlafaxine on p90Rsk activity in rat C6-gliomas and brain

The intracellular actions of the antidepressant, venlafaxine, were studied in C6-gliomas using a phosphoproteomics approach. Long-term pre-treatment of C6-gliomas with venlafaxine followed by an acute challenge with isoproterenol (a β-adrenoceptor agonist), resulted in increased p90Rsk phosphorylati...

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Veröffentlicht in:Neuroscience letters 2004-11, Vol.372 (1), p.99-103
Hauptverfasser: Khawaja, Xavier Z., Storm, Stephen, Liang, Jin-Jun
Format: Artikel
Sprache:eng
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Zusammenfassung:The intracellular actions of the antidepressant, venlafaxine, were studied in C6-gliomas using a phosphoproteomics approach. Long-term pre-treatment of C6-gliomas with venlafaxine followed by an acute challenge with isoproterenol (a β-adrenoceptor agonist), resulted in increased p90Rsk phosphorylation (three-fold) versus control levels (isoproterenol alone). The effect of venlafaxine pre-treatment on p90Rsk activity was dose-dependent (EC 50 = 3.75 nM) in C6 gliomas. In rat brain sections, intense immunoreactive phospho-p90Rsk labeling was observed for both neurons and glia, especially in cortical layers II/III and hippocampal formations. In vivo studies demonstrated an intense but similar distribution pattern of phospho-p90Rsk staining after chronic venlafaxine dosing of rats compared to naives and no region-specific drug effect was observed in vivo. In conclusion, our findings suggest that some of the centrally-mediated benefits of venlafaxine in depression may be due to its intracellular properties especially on the neuro-glial circuitry and MAPK/p90Rsk-dependent pathways at an early stage.
ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2004.09.029