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Histone Acetylation in the Nucleus Accumbens Shell Modulates Ethanol‐Induced Locomotor Activity in DBA /2 J Mice
Author(s) -
Sprow Gretchen M.,
Rinker Jennifer A.,
Thiele Todd E.
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12502
Subject(s) - nucleus accumbens , sensitization , trichostatin a , histone deacetylase , acetylation , chemistry , histone deacetylase inhibitor , histone , pharmacology , behavioral sensitization , histone h3 , histone h4 , neuroscience , biochemistry , biology , receptor , gene
Background A growing body of literature suggests that epigenetic mechanisms, including histone acetylation, may play key roles in drug abuse and the development of addiction. Experiments in this study were designed to investigate the role of histone acetylation in ethanol (Et OH )‐induced locomotor sensitization. Methods Immunohistochemical, Western blotting, and site‐directed pharmacological techniques were used to explore the roles of histone acetylation at histone H3 (acH3K9) in both the expression of and acquisition of Et OH ‐induced locomotor sensitization. A commonly used sensitization protocol, in which animals were exposed to repeated injections of a low dose of Et OH while in their home cage, was used to examine this behavioral phenomenon. Additionally, site‐directed administration of the histone deacetylase inhibitor ( HDAC i) Trichostatin A ( TSA ), in the absence of repeated Et OH injections, was used to examine the role of hyperacetylation in the nucleus accumbens ( NAC ) shell in Et OH ‐induced locomotor sensitization. Results Sensitized mice displayed elevated acH3K9 immunoreactivity ( IR ) localized to the shell of the NAC . This augmentation in acH3K9 IR was confirmed, in a separate experiment, using Western blot analyses. Next, repeated intra‐accumbal infusions of TSA , in the absence of repeated Et OH injections, were sufficient to induce an augmented locomotor response to a later injection of a low dose (2.0 g/kg, intraperitoneally) of Et OH , indicative of cross‐sensitization to this locomotor stimulation between TSA and Et OH . Finally, a local infusion of TSA into the shell of the accumbens was also associated with a significant increase in acH3K9 IR within this region. Conclusions Together, the present observations suggest that histone acetylation, particularly within the shell of the NAC , is important for the development and expression of Et OH ‐induced locomotor sensitization.