title: Vulnerability to opiate intake in maternally deprived rats: implication of MeCP2 and of histone acetylation.
abstract: We previously showed that maternal deprivation predisposes male rats to anxiety, accompanied with an increase in their opiate consumption. In the present report, we searched for brain epigenetic mechanisms that possibly underlie this increase. For that, we examined the expression of the methyl-CpG-binding protein MeCP2 and of the histone deacetylases HDAC2 and HDAC3, as well as the acetylation status of histone H3 and H4 in mesolimbic structures of adult maternally deprived rats, using immunohistochemistry and Western blot analysis. A long-lasting increase in MeCP2 expression was found throughout the striatum of deprived rats. Enhanced HDAC2 expression and increased nuclear HDAC activity in the nucleus accumbens of deprived rats were associated with lower acetylation levels of histone H3 and H4. Treatment for 3 weeks with the HDAC inhibitor sodium valproate abolished HDAC activation together with the decrease in the acetylation levels of histone H4, and was accompanied with normalized oral morphine consumption. The data indicate that epigenetic mechanisms induced by early adverse environment memorize life experience to trigger greater opiate vulnerability during adult life. They suggest that sodium valproate may lessen vulnerability to opiate intake, particularly in subgroups of individuals subjected to adverse postnatal environments.
authors: Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg, France.
authors: Carolina
authors: C
authors: Tesone-Coelho
authors: Lydie J
authors: LJ
authors: Morel
authors: Jeena
authors: J
authors: Bhatt
authors: Lucie
authors: L
authors: Estevez
authors: Laurent
authors: L
authors: Naudon
authors: Bruno
authors: B
authors: Giros
authors: Jean
authors: J
authors: Zwiller
authors: Valérie
authors: V
authors: Daugé
mesh_terms: D000107:Acetylation; D000701:Analgesics, Opioid; D000818:Animals; D001522:Behavior, Animal; D044127:Epigenesis, Genetic; D059647:Gene-Environment Interaction; D056464:Histone Deacetylase 2 / Q000235:genetics*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D008426:Maternal Deprivation; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009020:Morphine; D009714:Nucleus Accumbens / Q000378:metabolism; D009293:Opioid-Related Disorders / Q000235:genetics*; D051381:Rats; D014635:Valproic Acid / Q000494:pharmacology; D000099186:Histone Deacetylase 3
chemical_list: D000701:Analgesics, Opioid; D056464:Histone Deacetylase 2; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006657:Histones; D051783:Methyl-CpG-Binding Protein 2; D009020:Morphine; D014635:Valproic Acid; D000099186:Histone Deacetylase 3; C497394:Mecp2 protein, rat; C533426:Hdac2 protein, rat
keywords: HDAC; MeCP2; histone acetylation; maternal deprivation; morphine consumption; sodium valproate