Alcohol Use Disorder (AUD) is responsible each year for more than 2.5 million deaths worldwide, more than 58 million life years lost worldwide, and $220 billion financial cost in the United States alone. Post-Traumatic Stress Disorder (PTSD) affects 7.7 million Americans, and PTSD costs the U.S. billions of dollars annually. These problems will increase in scope during a time of perpetual U.S. involvement in overseas military conflicts. There is a lack of research directly investigating the neurobiology of traumatic stress-induced escalation of alcohol use. This proposal seeks to identify the neurobiological basis for alcohol abuse in individuals with PTSD, with the ultimate goal of contributing to the tailoring of effective therapeutic strategies to reduce alcohol drinking in humans with PTSD. This project falls within the scope of the NIAAA mission to support biomedical and behavioral research on the causes and treatment of alcoholism. More specifically, this application proposes the use of rat models to investigate the biological basis for excessive alcohol drinking following exposure to traumatic stress by using a multi-disciplinary approach that integrates behavior, pharmacology, molecular biology, and optogenetics techniques. This question is particularly important for the mission of the NIAAA because of the high rate of alcohol abuse in individuals with traumatic stress disorders, and the fact that AUD and PTSD each promote mortality and shorten life spans in humans. The long-term goals of this application are to understand the neurobiological basis of co-morbid AUD and PTSD, and to identify pharmacotherapies with promise for reducing alcohol abuse in individuals with PTSD. The proposed aims will investigate the role of amygdala neuropeptides and specific amygdala output pathways in mediating traumatic stress-induced alcohol drinking and negative affect. The overarching hypothesis of this proposal is that neuropeptides in the amygdala mediate traumatic stress-induced escalation of alcohol drinking.
Alcohol Use Disorder (AUD) and Post-Traumatic Stress Disorder (PTSD) are responsible for millions of deaths annually and cost the United States hundreds of billions of dollars, and humans with PTSD are 3-5 times more likely than the general population to develop AUD. Co-morbid AUD and PTSD promote mortality and shorten life spans in humans, but little is known about the neurobiological basis for the high rate of co-morbidity between these two disorders. This proposal seeks to understand the role of amygdala neuropeptides and amygdala output pathways in mediating stress-induced alcohol drinking, with the ultimate goal of tailoring pharmacotherapeutic strategies to reduce alcohol drinking in humans with PTSD.
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