Vulnerability to opiate intake in maternally deprived rats: implication of MeCP2 and of histone acetylation
| Autor: | Carolina Tesone-Coelho, Lucie Estevez, Bruno Giros, Lydie J. Morel, Jeena Bhatt, Laurent Naudon, J. Zwiller, Valérie Daugé |
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| Rok vydání: | 2013 |
| Předmět: |
Pharmacology
0303 health sciences medicine.medical_specialty biology Histone deacetylase 2 Medicine (miscellaneous) Nucleus accumbens Histone H4 03 medical and health sciences Psychiatry and Mental health Histone H3 0302 clinical medicine Histone Endocrinology Acetylation Internal medicine biology.protein medicine Epigenetics Opiate 030217 neurology & neurosurgery 030304 developmental biology |
| Zdroj: | Addiction Biology. 20:120-131 |
| ISSN: | 1355-6215 |
| DOI: | 10.1111/adb.12084 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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