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Regulation of cocaine-induced activator protein 1 transcription factors by the extracellular signal-regulated kinase pathway.

Abstract：

:Extracellular signal-regulated kinases and activator protein 1 transcription factor have been functionally linked to addiction. It has also been shown that extracellular signal-regulated kinase activation can regulate cocaine-induced expression of c-Fos and FosB, two possible components of activator protein 1. A direct link between extracellular signal-regulated kinases and activator protein 1 activation has, however, remained unexplored. In this study, we investigated the role of extracellular signal-regulated kinases in the regulation of DNA-binding activity and composition of activator protein 1 induced in the mouse caudate putamen by cocaine treatment. We have found that pre-treatment with SL327, a selective inhibitor the extracellular signal-regulated kinase pathway, has no influence on cocaine-induced DNA-binding activity of activator protein 1, when examined one hour after an acute cocaine treatment. This phenomenon results from simultaneous decrease of c-Fos protein level and increases in JunB and deltaFosB protein levels. SL327 pre-treatment, however, reduces the DNA-binding activity of the activator protein 1 complex induced six hours after an acute cocaine treatment as well as one hour after the last of the chronic cocaine injections, a phenomenon that results from the concomitant reduction of all cocaine-induced proteins (c-Fos, FosB, deltaFosB, JunB). In conclusion, we have found that extracellular signal-regulated kinase inhibition may not only interfere with cocaine-induced gene expression and activator protein 1 complex activation, but may also disturb the time-course of gene expression and composition of activator protein 1 complex. Our results support the notion that inhibitors of the extracellular signal-regulated kinase pathway could be valuable tools to obliterate cocaine-induced molecular changes and the development of addiction.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Radwanska K,Valjent E,Trzaskos J,Caboche J,Kaczmarek L

doi

10.1016/j.neuroscience.2005.09.001

keywords:

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

253-64

issue

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(05)01027-4

journal_volume

137

pub_type

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Regulation of cocaine-induced activator protein 1 transcription factors by the extracellular signal-regulated kinase pathway.