Patients diagnosed with posttraumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms that result from exposure to one or more traumatic events, with women having increased vulnerability for diagnosis; however, the mechanisms of this increased vulnerability remain unknown. The dorsal raphe nucleus (DRN) is a brain region that has been implicated in enhanced fear and anxiety-like behavior in rodents. This project investigated if antagonism of corticotropin releasing hormone (CRH) type 2 receptors in the DRN would eliminate the enhancement of fear learning in previously stressed animals. On postnatal day (PND) 17, rats were exposed to either 0 or 15 footshocks in Context A. On PND ~80, rats underwent intracranial surgery to place a cannula into the DRN. On PND ~90, rats were placed back into Context A for an 8-minute test in the absence of shock to assess memory of the aELS session. On PND ~91, animals were infused with a CRH2 receptor antagonist, K41498, or vehicle. Fifteen minutes following drug infusion, animals were placed into novel Context B for 1-footshock fear conditioning. The following day, freezing was assessed during a 5-minute test in the absence of footshock. We showed that animals that received aELS demonstrated SEFL regardless of acquisition drug infusion. This shows that CRH2 receptor signaling in the DRN may not be involved in SEFL. Future studies should assess the role of CRH1 receptor signaling in the DRN. With intentions of attending medical school following my graduation from Miami University, this research project has provided me with an abundance of learning opportunities such as becoming well-versed in intracranial surgery, infusions, behavior testing, intercardinal perfusions, and more. Above all, this work has not only given me insight into the ever-increasing prevalence of PTSD, but also the mechanisms that it manifests itself in on a molecular level.
Authors: Lauren Roos, Kennedy Seipel, Lucy Chappell, Kate Brand, Lily Buck, Brianna Minshall & Jennifer Quinn
Advisors: Jennifer Quinn, Department of Psychology
Brianna Minshall, Department of Psychology
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