The first two authors contributed equally to the work.
Blockade of Ethanol-Induced Behavioral Sensitization by Sodium Butyrate: Descriptive Analysis of Gene Regulations in the Striatum
Article first published online: 12 MAR 2013
Copyright © 2013 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 37, Issue 7, pages 1143–1153, July 2013
How to Cite
Legastelois, R., Botia, B. and Naassila, M. (2013), Blockade of Ethanol-Induced Behavioral Sensitization by Sodium Butyrate: Descriptive Analysis of Gene Regulations in the Striatum. Alcoholism: Clinical and Experimental Research, 37: 1143–1153. doi: 10.1111/acer.12088
- Issue published online: 3 JUL 2013
- Article first published online: 12 MAR 2013
- Manuscript Accepted: 19 NOV 2012
- Manuscript Received: 4 SEP 2012
- ANR (National Research Agency) SAMENTA 2011
- SENSIBALCO, the Conseil Régional de Picardie (CRP), the Interministerial Mission for the fight against drugs and drug addiction (MiLDT)-National Institute of Health and Medical Research (INSERM)-Institute of Cancer (InCa). Grant Number: APE09002ESA
- Institut de France/Fondation NRJ “Biology of addiction” and ERDF Grant/INTERREG IVA
- HDAC Inhibitor;
- Gene Expression
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.
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.
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.
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.