Chronic Stress and Neuronal Pathology: Neurochemical, Molecular and Genetic Factors
Abstract
The purpose of this proposal is to test the hypothesis that chronic stress produces lasting changes in brain dopamine function leading to permanent neuronal damage through oxidative mechanisms. Certain subject populations may be uniquely susceptible to this pathological cascade through hyperresponsiveness of the corticotropin releasing factor stress response system. To test this hypothesis, two specific aims are currently in progress: 1) To examine the effects of chronic stress on behavioral, neurochemical and molecular measures of neuronal pathology to the brain dopamine system; 2) To develop a phenotype of hyperresponsiveness of the CRF hypothalamic pituitary adrenal axis by selective breeding. The results show evidence of CRF induced hypoactivity in the brain dopamine system as measured by an increase in catalepsy and a decrease in amphetamine-induced stereotyped behavior that last up to four months. In addition, the first phase of selective breeding of rats hyperresponsive to stress has been accomplished. The initial separation in HPA axis activity showed a two- to four-fold difference between low and high responders. These results should ultimately provide not only key information about neuronal dysfunction produced by chronic stress but critical knowledge of the genetic/molecular factors that contribute to individual vulnerability to stress and its pathological consequences.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA382530
Entities
People
- George F. Koob
Organizations
- Scripps Research