The main objective of the current proposal is to examine the effects of post-traumatic stress disorder(PTSD) on alcohol dependence. The proposed career transition award will provide new training for theapplicant in animal models of PTSD and in biochemical techniques that will complement the applicant'sexperience with behavioral animal models of alcoholism. The training phase of the award will leave theapplicant prepared to lead an independent research program in the R00 phase of the award. The R00 phase ofthe award and the independent research career of the applicant beyond this award will continue to focus on thenegative reinforcement aspects of alcoholism and their neural overlap with other psychiatric disorders. Following exposure to a traumatic stressor, PTSD is a long-term pathological state marked by increases inanxiety and arousal, decreases in the ability to perceive pleasure, and generalization and avoidance of trauma-related stimuli. Alcohol dependence is compulsive alcohol use despite adverse consequences, loss of controlwhen taking alcohol, and development of tolerance that results in withdrawal symptoms in the absence of thedrug. Excessive alcohol consumption can be driven by the ability of the drug to alleviate aversive symptoms,including those produced by a pre-existing emotional disorder (e.g., PTSD). It is hypothesized that animals thatexhibit maladaptive stress responses will exhibit higher susceptibility to alcohol dependence. Because PTSDpatients and alcoholics exhibit similar patterns of neural dysregulation in the limbic system, it is hypothesizedthat the amygdala and BNST serve as a neural interface for overlapping/additive effects of PTSD and alcoholdependence. It is hypothesized that neuromodulators involved in the brain stress response (i.e. corticotropin-releasing factor [CRF], neuropeptide Y [NPY], and norepinephrine [NE]) and ubiquitous in these limbic circuitsare similarly and additively dysregulated in PTSD and alcohol dependence.
Individuals with pre-existing emotional disorders (e.g., PTSD) are highly vulnerable to develop alcohol dependence. This project will examine the overlapping neural mechanisms of PTSD and alcoholism that contribute to the similar behavioral dysregulation seen in the two disorders. A major goal of this project will be to pharmacologically block PTSD-induced increases in the vulnerability to develop alcohol dependence.
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