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

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• dc.contributor.author Valjent, Emmanuelca
• dc.contributor.author Corvol, Jean-Christopheca
• dc.contributor.author Pagès, Christianeca
• dc.contributor.author Besson, Marie-J.ca
• dc.contributor.author Maldonado, Rafael, 1961-ca
• dc.contributor.author Caboche, Jocelyneca
• dc.date.accessioned 2012-07-05T06:54:22Z
• dc.date.available 2012-07-05T06:54:22Z
• dc.date.issued 2000ca
• 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.description.sponsorship This work was supported by the University Pierre et Marie Curie and the Centre National de la Recherche Scientifique for J.C. and European Commission (BIOM ED-2 #98–227) for R.M. E.V. was supported by a grant from “La fondation des Treilles”. We are grateful to J.M.Trzaskos, J.L. Hytrek, A.C. Tabaka, J.S. Piecara, and C. Teleha for the generous gift of SL327.
• dc.format.mimetype application/pdfca
• 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. DOI: 10.1523/jneurosci.20-23-08701.2000ca
• dc.identifier.doi http://dx.doi.org/10.1523/jneurosci.20-23-08701.2000
• dc.identifier.issn 0270-6474ca
• dc.identifier.uri http://hdl.handle.net/10230/16672
• dc.language.iso engca
• dc.publisher Society for Neuroscienceca
• dc.relation.ispartof Journal of Neuroscience. 2000;20(23):8701-9
• dc.rights © 2000, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/20/23/8701ca
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• 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.subject.other Cocaïna -- Efectes fisiològics
• dc.subject.other Drogoaddicció -- Aspectes moleculars
• dc.title Involvement of the extracellular signal-regulated kinase cascade for cocaine-rewarding propertiesca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersion