The STRONG STAR Multidisciplinary PTSD Research Consortium
Abstract
The hypothesis addressed by this project is that early life exposure to stress or glucocorticoids produces a distinct neurochemical and behavioral phenotype characterized by life-long vulnerability to stressors that trigger PTSD. During the past year, we completed studies on our prenatal stress model (PNS). We found that PNS creates a sensitization to conditioned fear in the adult offspring, and a resistance to the extinction of conditioned fear, but only after prolonged adult stress. We also found that PNS causes a unique adult neurochemical and hormonal phenotype that suggests possible mechanisms by which it can increase vulnerability to traumatic stress during adulthood. A manuscript describing these results was published online June 22, 2011. We also began work on a second model to determine whether glucocorticoid receptor stimulation is necessary and sufficient for the behavioral and neurochemical phenotype produced by PNS. We began studies to determine the effects of administering the endogenous glucocorticoid, corticosterone (CORT), on the behavioral and neurochemical phenotypes produced by PNS. One study showed that a dose of corticosterone that reproduces the levels of CORT in dams and pups during prenatal stress demonstrates that the glucocorticoid antagonist, metyrapone (MET), blocks the elevation of CORT. In another study, we found that prenatal CORT did not reproduce the behavioral effects of PNS, possibly due to the use of DMSO as a vehicle. Prenatal CORT reproduced selected neurochemical effects of PNS, i.e,. reduction of glucocorticoid receptors in the adult prefrontal cortex. However, unlike PNS, it did not reduce TH mRNA in the brainstem region containing the locus ceruleus. We have begun another set of studies to increase the N and measure the effects of prenatal CORT on adult vulnerability to stress.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2011
- Accession Number
- ADA554007
Entities
People
- Alan Frazer
- David Morilak
- Randy Strong
Organizations
- University of Texas at San Antonio