Ethanol-Induced Locomotor Sensitization: NPY Signaling and Histone Acetylation in the Nucleus Accumbens and Striatum of DBA/2J Mice

Recent evidence indicates that neuropeptide Y (NPY) signaling modulates ethanol-induced locomotor sensitization. Additionally, a growing body of literature suggests that epigenetic mechanisms, including histone acetylation, may play important roles in drug addiction. In the present study, we used immunohistochemical techniques to investigate the expression of both NPY and the acetylation of histones H3 and H4 in the nucleus accumbens and striatum following the induction of locomotor sensitization. Mice sensitized to the locomotor stimulant effects of ethanol displayed increases in NPY in the dorsolateral striatum and increases in acetylated H3 in the nucleus accumbens shell. Interestingly, mice that received an acute injection of ethanol displayed decreases in NPY specific to the core of the nucleus accumbens. Finally, peripheral administration of Tricostatin A, a histone deacetylase inhibitor, augmented the acquisition, but not the expression, of locomotor sensitization. The present observations indicate involvement of NPY and histone acetylation in ethanol-induced locomotor sensitization.