title: Differential regulation of MeCP2 and PP1 in passive or voluntary administration of cocaine or food.
abstract: Cocaine exposure induces changes in the expression of numerous genes, in part through epigenetic modifications. We have initially shown that cocaine increases the expression of the chromatin remodeling protein methyl-CpG binding protein 2 (MeCP2) and characterized the protein phosphatase-1Cβ (PP1Cβ) gene, as repressed by passive i.p. cocaine injections through a Mecp2-mediated mechanism involving de novo DNA methylation. Both proteins being involved in learning and memory processes, we investigated whether voluntary cocaine administration would similarly affect their expression using an operant self-administration paradigm. Passive and voluntary i.v. cocaine intake was found to induce Mecp2 and to repress PP1Cβ in the prefrontal cortex and the caudate putamen. This observation is consistent with the role of Mecp2 acting as a transcriptional repressor of PP1Cβ and shows that passive intake was sufficient to alter their expression. Surprisingly, striking differences were observed under the same conditions in food-restricted rats tested for food pellet delivery. In the prefrontal cortex and throughout the striatum, both proteins were induced by food operant conditioning, but remained unaffected by passive food delivery. Although cocaine and food activate a common reward circuit, changes observed in the expression of other genes such as reelin and GAD67 provide new insights into molecular mechanisms differentiating neuroadaptations triggered by each reinforcer. The identification of hitherto unknown genes differentially regulated by drugs of abuse and a natural reinforcer should improve our understanding of how two rewarding stimuli differ in their ability to drive behavior.
authors.affiliation: Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR 7364 CNRS,Université de Strasbourg,Strasbourg,France.
authors.forename: Sarah Pol
authors.initials: SP
authors.lastname: Bodetto
authors.affiliation: Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR 7364 CNRS,Université de Strasbourg,Strasbourg,France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Romieu
authors.affiliation: Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR 7364 CNRS,Université de Strasbourg,Strasbourg,France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Sartori
authors.affiliation: Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR 7364 CNRS,Université de Strasbourg,Strasbourg,France.
authors.forename: Carolina
authors.initials: C
authors.lastname: Tesone-Coelho
authors.affiliation: Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR 7364 CNRS,Université de Strasbourg,Strasbourg,France.
authors.forename: Monique
authors.initials: M
authors.lastname: Majchrzak
authors.affiliation: Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR 7364 CNRS,Université de Strasbourg,Strasbourg,France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Barbelivien
authors.affiliation: Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR 7364 CNRS,Université de Strasbourg,Strasbourg,France.
authors.forename: Jean
authors.initials: J
authors.lastname: Zwiller
authors.affiliation: Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR 7364 CNRS,Université de Strasbourg,Strasbourg,France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Anglard
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004435:Eating / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005508:Food Deprivation / Q000502:physiology; D015870:Gene Expression; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D011897:Random Allocation; D017208:Rats, Wistar; D000091042:Reelin Protein; D012201:Reward; D012646:Self Administration; D012697:Serine Endopeptidases / Q000378:metabolism; D014836:Volition
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D018765:Dopamine Uptake Inhibitors; D016326:Extracellular Matrix Proteins; C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; D054645:Protein Phosphatase 1; D012697:Serine Endopeptidases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D003042:Cocaine