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 (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. Animal work is complete. The have been no changes in scope, but some delays due to personnel issues and methods refinements. Additional data analyses will likely reveal additional stress-PTSD-alcohol interactions.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2018
- Accession Number
- AD1072482
Entities
People
- Dennis Rasmussen
Organizations
- Seattle Institute for Biomedical and Clinical Research