title: Inhibition of corticotropin releasing factor expression in the central nucleus of the amygdala attenuates stress-induced behavioral and endocrine responses.
abstract: Corticotropin releasing factor (CRF) is a primary mediator of endocrine, autonomic and behavioral stress responses. Studies in both humans and animal models have implicated CRF in a wide-variety of psychiatric conditions including anxiety disorders such as post-traumatic stress disorder (PTSD), depression, sleep disorders and addiction among others. The central nucleus of the amygdala (CeA), a key limbic structure with one of the highest concentrations of CRF-producing cells outside of the hypothalamus, has been implicated in anxiety-like behavior and a number of stress-induced disorders. This study investigated the specific role of CRF in the CeA on both endocrine and behavioral responses to stress. We used RNA Interference (RNAi) techniques to locally and specifically knockdown CRF expression in CeA. Behavior was assessed using the elevated plus maze (EPM) and open field test (OF). Knocking down CRF expression in the CeA had no significant effect on measures of anxiety-like behavior in these tests. However, it did have an effect on grooming behavior, a CRF-induced behavior. Prior exposure to a stressor sensitized an amygdalar CRF effect on stress-induced HPA activation. In these stress-challenged animals silencing CRF in the CeA significantly attenuated corticosterone responses to a subsequent behavioral stressor. Thus, it appears that while CRF projecting from the CeA does not play a significant role in the expression stress-induced anxiety-like behaviors on the EPM and OF it does play a critical role in stress-induced HPA activation.
authors.affiliation: Avera Research Institute, Avera McKennan Hospital and University Health Center Sioux Falls, SD, USA ; Neuroscience Group, Division of Basic Biomedical Sciences, University of South Dakota Sanford School of Medicine Vermillion, SD, USA ; Department of Psychiatry, University of South Dakota Sanford School of Medicine Sioux Falls, SD, USA ; Research Service, Sioux Falls VA Health Care System Sioux Falls, SD, USA.
authors.forename: Leah B
authors.initials: LB
authors.lastname: Callahan
authors.forename: Kristi E
authors.initials: KE
authors.lastname: Tschetter
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Ronan
keywords: CRF; CeA; RNA interference; anxiety; corticosterone; knockdown; stress