Involvement of the extracellular signal-regulated kinase cascade for cocaine-rewarding properties

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Valjent E, Corvol JC, Pages C, Besson MJ, Maldonado R, Caboche J. Involvement of the extracellular signal-regulated kinase cascade for cocaine-rewarding properties. J Neurosci. 2000; 20(23): 8701-9
http://hdl.handle.net/10230/16672
To cite or link this document: http://hdl.handle.net/10230/16672
dc.contributor.author Valjent, Emmanuel
dc.contributor.author Corvol, Jean-Christophe
dc.contributor.author Pagès, Christiane
dc.contributor.author Besson, Marie-J.
dc.contributor.author Maldonado, Rafael
dc.contributor.author Caboche, Jocelyne
dc.date.accessioned 2012-07-05T06:54:22Z
dc.date.available 2012-07-05T06:54:22Z
dc.date.issued 2000
dc.identifier.citation Valjent E, Corvol JC, Pages C, Besson MJ, Maldonado R, Caboche J. Involvement of the extracellular signal-regulated kinase cascade for cocaine-rewarding properties. J Neurosci. 2000; 20(23): 8701-9
dc.identifier.issn 0270-6474
dc.identifier.uri http://hdl.handle.net/10230/16672
dc.description.abstract A central feature of drugs of abuse is to induce gene expression in discrete brain structures that are critically involved in behavioral responses related to addictive processes. Although extracellular signal-regulated kinase (ERK) has been implicated in several neurobiological processes, including neuronal plasticity, its role in drug addiction remains poorly understood. This study was designed to analyze the activation of ERK by cocaine, its involvement in cocaine-induced early and long-term behavioral effects, as well as in gene expression. We show, by immunocytochemistry, that acute cocaine administration activates ERK throughout the striatum, rapidly but transiently. This activation was blocked when SCH 23390 [a specific dopamine (DA)-D1 antagonist] but not raclopride (a DA-D2 antagonist) was injected before cocaine. Glutamate receptors of NMDA subtypes also participated in ERK activation, as shown after injection of the NMDA receptor antagonist MK 801. The systemic injection of SL327, a selective inhibitor of the ERK kinase MEK, before cocaine, abolished the cocaine-induced ERK activation and decreased cocaine-induced hyperlocomotion, indicating a role of this pathway in events underlying early behavioral responses. Moreover, the rewarding effects of cocaine were abolished by SL327 in the place-conditioning paradigm. Because SL327 antagonized cocaine-induced c-fos expression and Elk-1 hyperphosphorylation, we suggest that the ERK intracellular signaling cascade is also involved in the prime burst of gene expression underlying long-term behavioral changes induced by cocaine. Altogether, these results reveal a new mechanism to explain behavioral responses of cocaine related to its addictive properties.
dc.language.iso eng
dc.publisher Society for Neuroscience
dc.relation.ispartof J Neurosci. 2000; 20(23): 8701-9
dc.rights (c) 2000, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/20/23/8701
dc.subject.other Cocaïna -- Efectes fisiològics
dc.subject.other Drogoaddicció -- Aspectes moleculars
dc.title Involvement of the extracellular signal-regulated kinase cascade for cocaine-rewarding properties
dc.type info:eu-repo/semantics/article
dc.subject.keyword Cocaine
dc.subject.keyword ERK
dc.subject.keyword Elk-1
dc.subject.keyword C-fos expression
dc.subject.keyword Striatum
dc.subject.keyword Dopamine receptors
dc.subject.keyword Reward
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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