This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Stress-induced psychopathologies are major problems affecting society. Disorders ranging from post-traumatic stress disorder (PTSD), depression and sleep dysregulation to lapse and relapse in addiction all have stress as an etiological factor. The mechanisms underlying these stress-induced disorders are poorly understood. Corticotropin releasing factor (CRF) is a molecule in brain that has been implicated as a primary coordinator of an organism?s adaptive stress responses - including endocrine, autonomic and behavioral responses. Numerous brain regions have been implicated in CRF mediated stress responses. The central nucleus of the amygdala (CeA) is a major extrahypothalamic source of CRF and is known to mediate behavioral, emotional and physiological responses to fear and anxiety. The goals of this project are to elucidate the specific role of corticotropin releasing factor (CRF) from the CeA in central responses to stress. Students will be involved in specific experiments in which we will: 1. Determine if CRF from the CeA is involved in mediating stress-induced and anxiety-like behaviors. RNA interference (RNAi) will be used to locally silence CRF expression bilaterally in the CeA of adult rats. The rats will then be put through a battery of behavioral paradigms to measure motor and anxiety-like behaviors. These tests include the open field test, elevated plus maze, light-dark box, and acoustic startle.2. Determine if knocking down CRF expression from the CeA using RNAi decreases measures of neuroendocrine and autonomic activation in response to stress. Heart rate and blood pressure will be monitored employing radiotelemetry. Circulating levels of corticosterone and adrenocorticotropic hormone (ACTH) will also be measured.
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