There has been much recent interest in the relationship between stress, alcohol use disorders and relapse to alcohol use. Animal studies have consistently demonstrated a connection between a number of experimentally-induced stressors and both the initiation of alcohol use and reinstatement after a period of human laboratory procedures have been used to investigate the relationship between experimentally-induced stressors and craving, a likely precursor to relapse in real world situations. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, one of the main hormonal systems involved in the stress response, is seen with chronic alcohol consumption. This dysregulation may play a role in stress-reduced relapse. The endogenous opiate response system is also involved in the regulation of the HPA axis stress response and has been implicated in the pathophysiology of alcohol use disorders. Opiate antagonists, such as naltrexone, decrease alcohol craving and relapse in alcohol-dependent individuals and have effects on HPA axis function. Our research group is investigating the relationship between Post- traumatic Stress Disorder (PTSD) and alcohol use disorders. These disorders commonly co-occur and individuals with PTSD may use alcohol in an attempt to dampen traumatic memories and decrease painful symptoms of PTSD. Dysregulation of the HPA axis is a key pathophysiologic characteristic of PTSD. Our recent work indicates greater alcohol craving in alcoholism as compared to individuals with alcoholism only. In this component, the physiologic and subjective responsiveness (including alcohol craving) and response of the HPA axis to a stressful task will be explored in a group of individuals with alcohol dependence without PTSD, PTSD without alcohol dependence, and no PTSD or alcohol dependence. Following the initial stress task and procedure, subjects will be randomly assigned to receive 6 days of naltrexone or matching placebo and the stress task procedure will be repeated. In summary, this project is designed to build upon the ongoing research in the area of PTSD and alcohol use disorders by further exploration of the neurobiologic interface between alcoholism and PTSD. This study may provide valuable information about the role of the HPA axis and the opiate system in stress-induced relapse.
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