Expression of HDAC3-Y298H Point Mutant in Medial Habenula Cholinergic Neurons Has No Effect on Cocaine-Induced Behaviors

Histone deacetylase 3 (HDAC3) is one of the most highly expressed HDACs in the brain shown to be a negative regulator of long-term memory formation. HDAC3 has also been shown to be involved in cocaine-associated behaviors, demonstrated by manipulations in the nucleus accumbens. Previous studies have demonstrated that expression of a dominant negative of a key HDAC3 target gene, nuclear receptor subfamily 4 group A member 2 (NR4A2), in cholinergic neurons of the medial habenula (MHb) blocked reinstatement of cocaine-induced conditioned place preference (CPP) as well as cue-induced intravenous self-administration (IVSA). Together, these findings suggested that HDAC3 would also be important for MHb-dependent reinstatement of CPP and IVSA, which we examined in this study. Contrary to our hypothesis, our results found that expression of an HDAC3 deacetylase dead point mutant within the cholinergic neurons of the mouse MHb had no effect on reinstatement or other cocaine-induced behaviors.