title: Blockade of ethanol-induced behavioral sensitization by sodium butyrate: descriptive analysis of gene regulations in the striatum.
abstract: BACKGROUND
  Behavioral sensitization induced by repeated ethanol (EtOH) exposure may play a critical role in the development of alcohol dependence. Because recent data demonstrate that histone deacetylase inhibitor (HDACi) may be of interest in the treatment of addiction, we explored the effect of the HDACi sodium butyrate (NaB) on EtOH-induced behavioral sensitization (EIBS) in DBA/2J mice. We also investigated gene regulations in the striatum of sensitized mice using epigenetic- and signal transduction-related PCR arrays.
  
  
  METHODS
  Mice were injected with saline or EtOH (0.5 to 2.5 g/kg) once a day for 10 days. Mice received NaB (200 to 600 mg/kg) 30 minutes before each injection (prevention protocol) or once daily between days 11 and 16 (reversal protocol). At day 17, brains were removed 30 minutes after a saline or EtOH challenge to assess gene and proteins levels.
  
  
  RESULTS
  Only the intermediate EtOH doses (1.0 and 2.0 g/kg) were effective in inducing EIBS, and both doses were associated with specific gene regulations in the striatum. The induction of sensitization by 1.0 g/kg (but not 2.0 g/kg) EtOH was dose-dependently prevented or reversed by NaB. Among the 168 studied genes, EIBS blockade was associated with specific gene regulations (bcl-2, bdnf, hdac4, pak1, penk, tacr1, vip…) and changes in brain-derived neurotrophic factor in both striatum and prefrontal cortex.
  
  
  CONCLUSIONS
  These results indicate that EIBS is associated with specific gene regulations in the striatum depending on the EtOH dose and that NaB can be useful in blocking some long-lasting neuro-adaptations to repeated EtOH administrations.
authors.affiliation: INSERM ERI 24, Groupe de Recherche sur l'Alcool et les Pharmacodépendances (GRAP), UFR de Pharmacie, Structure Fédérative de Recherche CAP-Santé, Université de Picardie Jules Verne, Amiens, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Legastelois
authors.forename: Béatrice
authors.initials: B
authors.lastname: Botia
authors.forename: Mickaël
authors.initials: M
authors.lastname: Naassila
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D002087:Butyrates / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation; D051379:Mice; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology
chemical_list: D002087:Butyrates; D000431:Ethanol
keywords: Epigenetic; Ethanol; Gene Expression; HDAC Inhibitor; Sensitization