Chronic Stress and Neuronal Pathology: Neurochemical, Molecular and Genetic Factors
Abstract
The purpose of this project is to explore the effects of chronic activation of the brain corticotropin releasing factor (CRF) stress system and to investigate individual susceptiblity to this pathological cascade. It is our hypothesis that sustained central CRF activation results in damage to the brain dopamine system through oxidative mechanisms and that certain populations may be uniquely susceptible. In Specific Aim I, the goal is to selectively breed rats for high and low response to stressors on the basis of their hypothalamic pituitary adrenal axis response to footshock. Two independent lines (replications) are being bred (the fifth generation of Line 1 is currently in utero and the third generation of Line 2 is nearing weaning). The lines appear to be separating at a steady, although moderate, rate, possibly reflecting a locking in of the original selection. In Specific Aim 2, the goal is to explore the effects of chronic hyperactivity of the brain CRF stress system on dysregulation of brain monoamine systems with a focus on dopamine. Chronic hyperactivity of the CRF system by repeated central administration of CRF produced a temporary dysfunction of the mesocortical and nigrostriatal dopaminergic systems possibly mediated by oxidative damage.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA400462
Entities
People
- George F. Koob
Organizations
- Scripps Research