Rodents provide a useful translational model of fear- and anxiety-related behaviors. Previously stressed animals exhibit physiological and behavioral stress responses that parallel those observed in anxious humans. 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 bed nucleus of the stria terminalis (BNST) is a brain region best known for its involvement in fear and anxiety. Current models indicate that PTSD involves a complex network of highly interconnected brain regions, including the BNST. However, the precise circumstances that engage it, and the brain mechanisms that mediate its involvement in PTSD are not fully known. Serotonin release into the BNST yields increased expression of both fear and anxiety, specifically through the 5-HT2C receptor. This project investigated whether serotonin signaling through its 5-HT2C receptor in the BNST is necessary for the stress-enhancement of adult fear learning that is observed in animals previously exposed to acute early life stress. Rats received 0 or 15 footshocks on postnatal day (PND)17. On PND80, rats underwent surgery to implant cannulae bilaterally into the BNST. On PND91, rats received bilateral infusions of vehicle, a 5-HT2C receptor antagonist (RS-102221) or a 5-HT2C receptor agonist (MK-212) prior to 1-footshock fear conditioning in a novel context. The next day, rats were returned to the fear conditioning context to assess their fear response (freezing). Results demonstrate that RS-102221 eliminated enhanced fear learning compared to controls and MK-212 in previously stressed females. Male groups were not significantly different from one another. Future studies should determine whether such alterations in serotonergic signaling yield changes in the activity of BNST corticotropin-releasing hormone (CRH) neurons.
Author: Catherine Wasylyshyn
Advisor: Jennifer Quinn, Psychology
Graduate Advisor: Brianna Minshall, Psychology
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