Early evidence supporting the involvement of HDACs in the stress response and antidepressant action showed that mice exposed to chronic social defeat stress experienced a temporary reduction followed by a lasting escalation in histone acetylation levels (H3K14ac), which was connected to decreased histone deacetylase 2 (HDAC2) levels in the NAc.130 Infusion of HDAC inhibitors (i.e., MS-275) into the NAc reversed global gene expression patterns in the NAc and improved depression-like behaviors. This evidence concerns the gene HDAC9 and major depressive disorder.