title: MeCP2 regulates ethanol sensitivity and intake.
abstract: We have investigated the expression of chromatin-regulating genes in the prefrontal cortex and in the shell subdivision of the nucleus accumbens during protracted withdrawal in mice with increased ethanol drinking after chronic intermittent ethanol (CIE) vapor exposure and in mice with a history of non-dependent drinking. We observed that the methyl-CpG binding protein 2 (MeCP2) was one of the few chromatin-regulating genes to be differentially regulated by a history of dependence. As MeCP2 has the potential of acting as a broad gene regulator, we investigated sensitivity to ethanol and ethanol drinking in MeCP2(308/) (Y) mice, which harbor a truncated MeCP2 allele but have a milder phenotype than MeCP2 null mice. We observed that MeCP2(308/) (Y) mice were more sensitive to ethanol's stimulatory and sedative effects than wild-type (WT) mice, drank less ethanol in a limited access 2 bottle choice paradigm and did not show increased drinking after induction of dependence with exposure to CIE vapors. Alcohol metabolism did not differ in MeCP2(308/) (Y) and WT mice. Additionally, MeCP2(308/) (Y) mice did not differ from WT mice in ethanol preference in a 24-hour paradigm nor in their intake of graded solutions of saccharin or quinine, suggesting that the MeCP2(308/) (Y) mutation did not alter taste function. Lastly, using the Gene Set Enrichment Analysis algorithm, we found a significant overlap in the genes regulated by alcohol and by MeCP2. Together, these results suggest that MeCP2 contributes to the regulation of ethanol sensitivity and drinking.
authors: Molecular and Integrative Neuroscience Department, The Scripps Research Institute, La Jolla, CA, USA.
authors: Vez
authors: V
authors: Repunte-Canonigo
authors: Jihuan
authors: J
authors: Chen
authors: Celine
authors: C
authors: Lefebvre
authors: Tomoya
authors: T
authors: Kawamura
authors: Max
authors: M
authors: Kreifeldt
authors: Oan
authors: O
authors: Basson
authors: Amanda J
authors: AJ
authors: Roberts
authors: Pietro Paolo
authors: PP
authors: Sanna
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002843:Chromatin / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D057898:Hemizygote; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D008810:Mice, Inbred C57BL; D009714:Nucleus Accumbens / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D013649:Taste / Q000187:drug effects
chemical_list: D002492:Central Nervous System Depressants; D002843:Chromatin; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D000431:Ethanol
keywords: Alcohol dependence; chromatin; epigenetic; gene regulation