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<dc:title xml:lang="fr">L'activation de la voie du GMP cyclique réduit le comportement d'auto-administration de cocaïne chez le rat : implication de régulations épigénétiques</dc:title>
<dcterms:alternative xml:lang="en">Activation of the cyclic GMP pathway reduces cocaine self-administration in rats : implication of epigenetic regulations</dcterms:alternative>
<dc:subject xml:lang="fr">Cocaïne</dc:subject>
<dc:subject xml:lang="fr">Auto-administration</dc:subject>
<dc:subject xml:lang="fr">GMPc</dc:subject>
<dc:subject xml:lang="fr">Épigénétique</dc:subject>
<dc:subject xml:lang="en">Cocaine</dc:subject>
<dc:subject xml:lang="en">Self-administration</dc:subject>
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<dc:subject xml:lang="en">Epigenetics</dc:subject>
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<dcterms:abstract xml:lang="fr">Nous avons étudié l'influence de la voie du cGMP sur le comportement d'auto-administration de cocaïne chez le rat. Les injections, dans le cortex préfrontal médian, de trois activateurs différents de cette voie diminuent le nombre d'injections que les rats déclenchent, indiquant une réduction de l'effet renforçant de la cocaïne et de leur motivation pour la drogue. Des études immunohistochimiques nous ont permis de mettre en évidence que cette effet comportemental s'accompagnait d'une diminution de l'expression de marqueurs épigénétiques (MeCP2, HDAC2) et d'une augmentation des niveaux d'acétylation des histones. Des résultats complémentaires confirment que la voie du cGMP est bien en mesure de réguler des protéines impliquées dans les mécanismes épigénétiques. La découverte d'une action via ces régulations nous permet de suggérer des pistes originales quant aux phénomènes mis en jeu dans la diminution observée des propriétés renforçantes de la cocaïne.</dcterms:abstract>
<dcterms:abstract xml:lang="en">We studied the influence of the cGMP pathway on cocaine self-administration by rats. When injected in the medial prefrontal cortex, three distinct activators of this pathway reduced the number of self-injections triggered by rats, suggesting a reduction of the reinforcing properties of cocaine and a lesser motivation of the animals for the drug. Immunohistochemical studies revealed that this behavioural effect was accompanied by a reduced expression of epigenetic markers (MeCP2, HDAC2), as well as inceased levels of histone acetylation. Complementary results indicate that the cGMP pathway is indeed able to regulate proteins implied in epigenetic mechanisms. The uncovering of an implication of these types of regulations leads us to suggest original hypotheses about the processes underlying the reduction of the reinforcing properties of cocaine.</dcterms:abstract>
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