Improving Performance Efficiency in the Warfighter
Abstract
The goal of this project is to design novel compounds that selectively bind estrogen receptor beta (ER(3) to alleviate fear and anxiety-related behaviors and enhance cognitive function ER(3 is a recently described member of the steroid/thyroid hormone receptor superfamily Although it was originally cloned and named based on homology to the classic estrogen receptor (a) ER(3 does not appear to be a critical component of reproductive physiology For example ER(3-knockout-mice have few reproductive deficits in contrast to ERa-knockout mice which are sterile Despite its name ER(3 is not exclusively a receptor for estrogen ER(3 can bind a number of other hormones and recent studies suggest that in males ER(3 is the functional receptor for 5a-androstane-3(3 17(3-diol (3(3-diol) an endogenous metabolite of the testicular androgen dihydrotestosterone ER(3 is also synthesized in brain with a distribution that gives clues to its function: ER(3 is found at high levels in areas that regulate stress responses and cognitive function Consistent with this ER(3 knockout mice show increased anxiety- related behaviors and reduced cognitive function Our preliminary findings described in the original application support this possibility Acute administration of the non-steroidal ER(3 selective agonist diarylpropionitrile (DPN) dramatically reduces anxiety related behaviors in female AND male rats when examined in behavioral tests such as the elevated plus maze and open field test DPN treatment also potently inhibits the hormonal responses to physical and psychological stressors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2007
- Accession Number
- ADA477152
Entities
People
- T. J. Wu