In Drosophila, changes in histone acetylation have also been implicated in the molecular and behavioral responses to the volatile organic solvent, benzyl alcohol [65]. Many organic solvents are abused as inhalants, which often induce rapid drug tolerance, thereby increasing the amount of drug needed to attain an equivalent behavioral effect. Ultimately, tolerance to inhalants can result in addiction and severe neurotoxicity. In Drosophila, a key mechanism involved in benzyl alcohol tolerance is the upregulation of slo, a Ca2+-activated K+ channel [66]. Induction of slo is associated with increases in histone H4 acetylation on its promoter, which is likely important for gene activation because pharmacological inhibition of HDAC activity increased both slo gene acetylation and mRNA expression [65]. Moreover, HDAC inhibition potentiated tolerance to benzyl alcohol, which further implicates histone acetylation in the behavioral responses to drugs of abuse.
