Numerous studies have demonstrated that HDAC inhibitors reduce ethanol intake after chronic ethanol exposure and during relapse after abstinence. However, the effect of an HDAC activator still unknown. In the present study we identified a molecule that induces an increase in total nuclear HDAC activity and a decrease in H4K12 acetylation level in SH-SY5Y cells after 48h treatment. We tested the effect of the i.c.v. injection of this molecule in rats drinking ethanol in the 20% ethanol intermittent 2-bottle choice procedure. Results were analyzed in low level and high level drinking animals and we found the HDAC activator significantly increased ethanol intake specifically in animals displaying low level ethanol drink- ing. The effect of the molecule in low drinkers was seen after only one injection and both after 2h and 24h after injection. We also measured the level of HDAC2, of H4K12 acetylation and the expression of GluN2A/ GluN2B subunits in different brain structures (prefrontal cortex, nucleus accumbens, dorsolateral striatum and dorsomedial striatum) of ethanol drinking rats before and after treatment with the HDAC activator, using the flow cytometry technique. Our results showed an increased in mean fluorescence intensity (but not of % of cells expressing HDAC2) in high drinkers, and specifically in the prefrontal cortex) with no significant effect of the HDAC activator. Our results also showed a decreased in mean fluorescence intensity (but not of % of cells expressing Ac-H4K12) in high drinkers, and specifically in the prefrontal cortex) with no significant effect of the HDAC activator. No significant differences were observed regarding the GluN2A/GluN2B subunits.