Adolescent Alcohol Abuse, Traumatic Stress, and Vulnerability to Development of PTSD

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7. PROJECT SUMMARY/ABSTRACT Post-Traumatic Stress Disorder (PTSD) and Alcohol Use Disorder (AUD) are two of the most prevalent psychiatric conditions and are highly comorbid. The social and financial burden that results from a lack of effective treatments for these disorders is enormous. Therefore, there is a clear and urgent need to gain a greater understanding of the pathophysiological basis of PTSD and AUD comorbidity. Current evidence suggests the neurocircuitry of PTSD and AUD significantly overlap, which includes dysfunctional control of behavior by the prefrontal cortex (PFC). Thus, alterations in prefrontal mediated cognitive processes that regulate behavior may contribute to the high comorbidity of the disorders. There is a strong correlation between the age of onset of alcohol use during adolescence and the likelihood of developing an AUD later in life. In addition, adolescence is a critical period of continued development, and accumulating evidence indicates that the abuse of alcohol during adolescence can have long-term consequences on brain and behavior. Considering the high prevalence of adolescent alcohol abuse, it is therefore surprising that little research has focused on understanding its impact on an individual’s ability to cope with a traumatic stress event in adulthood. The overarching hypothesis of this proposal is that adults with a history of adolescent alcohol abuse who experience a traumatic stress event have reduced stress resiliency and are at a significantly higher risk of developing PTSD and AUD. This experimental approach takes advantage of a binge ethanol model consisting of repeated cycles of Adolescent Intermittent Ethanol (AIE) exposure by vapor inhalation and a Single Prolonged Stress (SPS) procedure that is thought to model a traumatic stress event in humans. Following AIE and SPS exposure in early adulthood, rats will then be tested for alterations in fear behavior and ethanol self-administration. The following three specific aims are designed to test the overarching hypothesis: Aim 1 will test the hypothesis that exposure to AIE-SPS results in pharmacologically reversible alterations in fear-related behaviors. Aim 2 will test the hypothesis that exposure to AIE-SPS increases alcohol consumption and relapse-like behavior induced by exposure to fear conditioned cues. Aim 3 will test the hypothesis that AIE-SPS induced alterations of fear behaviors reflect alterations in prelimbic and infralimbic communication with core regions of the fear neurocircuitry. Findings from these novel and innovative studies will significantly advance our understanding of the behavioral deficits and neural mechanisms underlying the complex interactions between AUD and PTSD, and whether a history of adolescent alcohol abuse may represent a pre-existing risk factor that increases susceptibility of developing not only PTSD associated with a traumatic event but also AUD.