Involvement of the Extracellular Signal-Regulated Kinase Cascade for Cocaine-Rewarding Properties

• DOI: 10.1523/jneurosci.20-23-08701.2000
• Publication Date: 2018-04-05T15:10:58Z
• Authors: Emmanuel Valjent; Jean-Christophe C...; Christiane Pagès; Marie-Jo Besson; Rafael Maldonado; Jocelyne Caboche
• Keywords: Raclopride; Immediate early gene; Conditioned place preference

A central feature of drugs abuse is to induce gene expression in discrete brain structures that are critically involved behavioral responses related addictive processes. Although extracellular signal-regulated kinase (ERK) has been implicated several neurobiological processes, including neuronal plasticity, its role drug addiction remains poorly understood. This study was designed analyze the activation ERK by cocaine, involvement cocaine-induced early and long-term effects, as well expression. We show, immunocytochemistry, acute cocaine administration activates throughout striatum, rapidly but transiently. blocked when SCH 23390 [a specific dopamine (DA)-D1 antagonist] not raclopride (a DA-D2 antagonist) injected before cocaine. Glutamate receptors NMDA subtypes also participated activation, shown after injection receptor antagonist MK 801. The systemic SL327, a selective inhibitor MEK, abolished decreased hyperlocomotion, indicating this pathway events underlying responses. Moreover, rewarding effects were SL327 place-conditioning paradigm. Because antagonized c-fos Elk-1 hyperphosphorylation, we suggest intracellular signaling cascade prime burst changes induced Altogether, these results reveal new mechanism explain properties.