Birkle 9723900 Developing organisms are sensitive to various influences; exposure at critical times during development can permanently affect behavior and metabolism. In humans, psychosocial stress in expectant mothers is associated with developmental lag and behavioral disturbances in their children. When pregnant rats are stressed, their offspring develop the prenatal stress syndrome, characterized by abnormal behavioral and physiological responses to fear-provoking stimuli. Offspring of stressed rats (i.e., prenatally stressed rats) are less capable of coping with stress, and therefore respond to stressful stimuli to a greater degree. The working hypothesis of this project is that prenatal stress imprints the organizing brain during critical stages of prenatal development, creating effects that remain with the animal and alter the input, processing and behavioral responses to stimuli. This project will determine mechanisms for these effects by investigating the imprint of prenatal stress on the development of a neuropeptide system that could mediate the increased fearfulness and increased stress response observed in the offspring of stressed rats. This project will investigate neurochemical mechanisms for long-lasting developmental effects of prenatal stress. The research will focus on a specific neuropeptide in the brain, corticotropin releasing factor (CRF). CRF is a well-established mediator of both physical and mental responses to stress. The project will study changes in CRF in prenatally stressed offspring as compared to offspring of unstressed dams. The proposed experiments will localize changes in CRF content and CRF mRNA in specific regions and nuclei of the brain. These experiments will evaluate age of offspring as major variable. A develop mental change in CRF may be due to alterations in the regulation of CRF synthesis or release. In other words, the effects of prenatal stress on CRF systems may be secondary to changes in the responses to o ther hormones or neurotransmitters. The proposed experiments will investigate the effects of stress and drugs on CRF mRNA, CRF content and CRF release in prenatally stressed rats as compared to normal rats. The results of the proposed experiments will contribute to our understanding of the developmental neurobiology of the most basic emotion, fear. These studies may also reveal linkages between maternal stress and the production of offspring that are vulnerable to stress-related diseases and mental illness.
