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Stress and PTSD Mechanisms as Targets for Pharmacotherapy of Alcohol Abuse, Addiction and Relapse

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Seattle Institute For Biomedical And CLI Seatle United States

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We have demonstrated that 1 alcohol-nave rats exhibiting high acoustic startle response associated with increased anxiety-like behavior develop increased subsequent alcohol intake and preference which are correlated with acoustic startle response determined before initial alcohol access, providing a prospective index of vulnerability to developing alcohol abuse, as well as insights into mechanism 2 suppression of noradrenergic signaling decreases alcohol drinking in rats with a history of traumatic stress, but not in rats without this stress history informing clinical studies in which subjects exhibit variable responses to prazosin 3 this treatment also suppresses alcohol drinking by rats with history of compulsive-like alcohol drinking, but increases alcohol drinking by rats that do not these results inform clinical studies in which subjects have been reported to exhibit opposite responses that are dependent on family history of compulsive alcohol drinking 4 suppression of noradrenergic signaling at the time of traumatic stress decreases acquisition of increased voluntary alcohol drinking long after the stress, which provides a new model for preventive treatment. Accomplishment 1 has been published, 2-4 are in preparation for publication. All remaining proposed studies are currently in progress as planned, with no changes in scope, although with some delays due to personnel changes and due to the need for some methodology refinements.

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Technical Report,30 Sep 2016,29 Sep 2017



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Approved For Public Release;

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