How is my dissertation research relevant to current medical conditions?

Post-traumatic Stress Disorder (PTSD) continues to be a debilitating psychiatric disorder with limited treatment options. Lifetime prevalence of PTSD is around 7.8% in the general population with women being twice as likely as men to develop PTSD after experiencing a traumatic event. Traumatic stress disorder symptoms are classified in four clusters that include negative affect, intrusive thoughts and memories of the traumatic event, hyperarousal, and avoidance of contexts and stimuli associated with the trauma. Patients with PTSD are at a higher risk of developing comorbid conditions such as substance use disorders than patients without PTSD. Patients with substance use disorders, particularly cocaine use disorder (CUD), present with more severe PTSD symptoms and poorer responses to PTSD treatments. Cocaine is the third most abused drug in the U.S. with over 1.1 million people meeting criteria for cocaine use disorder and an average of 4,000 people overdosing from cocaine annually. Cocaine use poses a substantial economic and health burden with approximately 40% of drug-related emergency room visits involving cocaine and 25% of said visits being directly caused by cocaine abuse. Patients who use cocaine show higher rates of experiencing a traumatic event (43% of cocaine users) and higher rates of developing PTSD as compared to other abused substances. The rate of PTSD among cocaine users is approximately twice that of PTSD among the general population. Women exhibit higher rates of cocaine dependence. Among those seeking treatment for cocaine addiction, 30.2% of women and 15.2% of men meet criteria for PTSD. Also shown, 42.9% of cocaine users present with lifetime incidence of PTSD, and 22% of current cocaine users present with current PTSD diagnoses. Cocaine users with PTSD presented with younger age of first trauma exposure and higher prevalence of sexual assault compared to PTSD patients without CUD11. Currently the specific mechanisms underlying the development of CUD in those living with PTSD are unclear. 

Scientific premise: The proposed project is based on literature that demonstrates that stress (i.e. predator odor stress, social stress, early-life stress, and foot-shock) produces persistent hyperarousal, higher anxiety-like behavior, and elevated cocaine seeking behavior. This project will attempt to elucidate a potential mechanism for stress effects on behavior, including escalation of cocaine self-administration, using a rat model. Although we have known for some time that central amygdala (CeA) corticotropin releasing factor (CRF) is important for mediating stress effects and behaviors associated with cocaine use, a major gap in the field has been a lack of understanding of what the specific role of extrahypothalamic CRF is on stress-induced compulsive cocaine seeking. Here we will test our overarching hypotheses that CeA CRF mediates stress-induced increases in long access cocaine self-administration in Avoider rats and that these effects will be greater in female rats. Both stress and CUD are associated with dysregulation of the amygdala; patients with stress disorders and/or CUD show amygdala hyperactivity. Animals exposed to stress (i.e., foot-shock) show increased CRF signaling and CRF mRNA synthesis in the CeA. Rats that show persistent avoidance of a predator odor-paired context have significantly more CRF peptide content in the CeA for weeks after exposure to the stressor. Furthermore, intra-CeA CRF infusions in experimentally naïve animals induce conditioned place avoidance of a CRF-paired context (references available upon request).

Substance Abuse and Mental Health Services Administration Hotline: 800-662-4357