Brain CRF systems are important in integrating endocrine, autonomic, and behavioral responses to stress. Preclinical and clinical research suggests an important involvement of CRF systems and the amygdala in mediating symptoms associated with anxiety disorders and depression. CRF containing cell bodies and fibers, as well as the CRF binding protein and CRF receptors are found throughout the amygdala. The investigators have found that the major site of outflow from the amygdala, the central nucleus (CeA), is a brain site where endogenous CRF systems mediate stress-induced behavioral responses. Using site specific administration of a CRF antagonist (CRFa), they demonstrated that CRF receptors in the region of the CeA mediate acute and conditioned freezing behavior. Complementing these studies, they demonstrated that acute stress exposure results in increased amygdala CRF mRNA concentrations. This is the first direct evidence demonstrating that stress activates amygdaloid CRF systems. The overall aim of this proposal is to continue studies examining the role of amygdaloid CRF systems in mediating behavioral responses to stress. The investigators will characterize the effects of stress on the activation of the genes for CRF, its receptor, and its binding protein. The studies will provide important hypotheses regarding the role of CRF systems in mediating pathological anxiety, and other forms of human psychopathology.
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