Exploring the use of histone deacetylase inhibitors in treating rodent models of post-traumatic stress disorder and addiction

A large body of evidence shows that prolonged stress or even a single traumatic experience can lead to neurobiological and behavioral changes that are persistent. These changes have many deleterious long-term consequences and can lead to the development of post-traumatic stress disorder (PTSD). PTSD is associated with epigenetic changes that result in altered gene expression and subsequent protein synthesis. These epigenetic changes may account for the development of the disease itself in the form of exaggerated fear responses to neutral or mild stimuli and may render individuals more susceptible to the use and subsequent dependence on drugs of abuse. Substance use disorders (SUDs) similarly evoke persistent changes in gene expression that are mediated by epigenetic mechanisms. Because both PTSD and SUDs involve a memory component and an inability to extinguish unwanted behavioral responses, similar epigenetic changes may underlie long-term memory effects in both anxiety disorders and addiction.This dissertation work focuses on this interaction, emphasizing how an epigenetic approach to memory suppression may be a useful avenue to pursue in designing treatments for disorders that involve failures of inhibition, such as PTSD and substance abuse.