Blockade of Ethanol-Induced Behavioral Sensitization by Sodium Butyrate: Descriptive Analysis of Gene Regulations in the Striatum.

Background Behavioral sensitization induced by repeated ethanol ( Et OH) 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 ( Na B) on Et OH-induced behavioral sensitization ( EIBS) in DBA/2 J 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 Et OH (0.5 to 2.5 g/kg) once a day for 10 days. Mice received Na B (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 Et OH challenge to assess gene and proteins levels. Results Only the intermediate Et OH 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) Et OH was dose-dependently prevented or reversed by Na B. 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 Et OH dose and that Na B can be useful in blocking some long-lasting neuro-adaptations to repeated Et OH administrations. [ABSTRACT FROM AUTHOR]