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

Abstract : We have demonstrated that (1) alcohol-naive rats exhibiting high acoustic startle response (which is associated with increased anxiety-like behavior) develop increased subsequent alcohol intake and preference which are highly correlated with acoustic startle amplitude determined before the initial access to alcohol, providing a prospective index of vulnerability to developing alcohol abuse, as well as insights into mechanism. We have also demonstrated that (2) suppression of noradrenergic signaling decreases alcohol drinking in rats with a history of traumatic stress, butt not in rats without this stress history. This result informs clinical studies in which subjects are reported to exhibit variable responses to this treatment. In addition, we have demonstrated (3) that 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 (these results were presented at the 2016 Research Society on Alcoholism meeting). Accomplishment 1 has been published, 2 and 3 are in preparation for publication. all remaining proposed studies using rat models to address stress and PTSD mechanisms as targets for pharmacotherapy of PTSD and associated alcohol abuse 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.