title: Repeated Exposure to D-Amphetamine Decreases Global Protein Synthesis and Regulates the Translation of a Subset of mRNAs in the Striatum.
abstract: Repeated psychostimulant exposure induces persistent gene expression modifications that contribute to enduring changes in striatal GABAergic spiny projecting neurons (SPNs). However, it remains unclear whether changes in the control of mRNA translation are required for the establishment of these durable modifications. Here we report that repeated exposure to D-amphetamine decreases global striatal mRNA translation. This effect is paralleled by an enhanced phosphorylation of the translation factors, eIF2α and eEF2, and by the concomitant increased translation of a subset of mRNAs, among which the mRNA encoding for the activity regulated cytoskeleton-associated protein, also known as activity regulated gene 3.1 (Arc/Arg3.1). The enrichment of Arc/Arg3.1 mRNA in the polysomal fraction is accompanied by a robust increase of Arc/Arg3.1 protein levels within the striatum. Immunofluorescence analysis revealed that this increase occurred preferentially in D1R-expressing SPNs localized in striosome compartments. Our results suggest that the decreased global protein synthesis following repeated exposure to D-amphetamine favors the translation of a specific subset of mRNAs in the striatum.
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), UMR-5203, Institut de Génomique FonctionnelleMontpellier, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1191Montpellier, France; Université de Montpellier, UMR-5203Montpellier, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Biever
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), UMR-5203, Institut de Génomique FonctionnelleMontpellier, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1191Montpellier, France; Université de Montpellier, UMR-5203Montpellier, France.
authors.forename: Jihane
authors.initials: J
authors.lastname: Boubaker-Vitre
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), UMR-5203, Institut de Génomique FonctionnelleMontpellier, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1191Montpellier, France; Université de Montpellier, UMR-5203Montpellier, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Cutando
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), UMR-5203, Institut de Génomique FonctionnelleMontpellier, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1191Montpellier, France; Université de Montpellier, UMR-5203Montpellier, France.
authors.forename: Irene
authors.initials: I
authors.lastname: Gracia-Rubio
authors.affiliation: Department of Neuroscience, Memory and Brain Research Center, Baylor College of Medicine, Houston TX, USA.
authors.forename: Mauro
authors.initials: M
authors.lastname: Costa-Mattioli
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), UMR-5203, Institut de Génomique FonctionnelleMontpellier, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1191Montpellier, France; Université de Montpellier, UMR-5203Montpellier, France.
authors.forename: Emma
authors.initials: E
authors.lastname: Puighermanal
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), UMR-5203, Institut de Génomique FonctionnelleMontpellier, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1191Montpellier, France; Université de Montpellier, UMR-5203Montpellier, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Valjent
keywords: Arc/Arg3.1; D-amphetamine; eIF2α; protein synthesis; striatum; translation factors