Post-Stress Combined Administration of Beta-Receptor and Glucocorticoid Antagonists as a Novel Preventive Treatment in an Animal Model of PTSD
Abstract
Many PTSD symptoms reflect pathologically enhanced memory of traumatic stress. Stress-induced secretion of brain norepinephrine and glucocorticoids (GC) activate Beta-receptors and GC-receptors in the amygdala, enhancing consolidation of emotional memories. We hypothesized that giving a Beta-antagonist plus a GC-antagonist immediately after stress might decrease the strength of those associations, and prevent the emergence of PTSD. The goals of this work were to (1) validate a reliable model of PTSD amenable to testing acute drug treatment; (2) establish a reliable and valid test battery of PTSD-like behaviors in rats, including fear conditioning and extinction; and (3) test the combined drug treatment using the established model. Although we developed a reliable test battery for PTSD-like behavior, it proved more challenging to establish a consistent, reliable and valid model inducing PTSD-like behaviors. The proposed massed footshock model, derived from the literature, failed to affect the most relevant behavioral measures, and confounded fear conditioning. A modified Single Prolonged Stress model, also from the literature, was more promising but had only modest effects. Early results using a new combined Chronic + Acute Prolonged Stress (CAPS) model, incorporating both chronic and acute features of stress often associated with PTSD, were very promising, but mixed results were obtained with the acute drug interventions. Propranolol had no effect, and mifepristone had only a modest effect on extinction. Nonetheless, this project has been very productive, as we will continue to use this model in other ongoing studies. If PTSD is indeed best modeled by a combined chronic + acute stress, acute drug intervention may not be a feasible strategy.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2010
- Accession Number
- ADA538521
Entities
People
- David Morilak
Organizations
- University of Texas at San Antonio