Early life stress alters future stress responses by leading to neuropsychiatric disorders, such as post-traumatic stress disorder and anxiety disorders. Following exposure to a stressor, animals release hormones that aim to reinstate homeostasis. Corticosterone (CORT), a stress hormone, is associated with the consolidation of fear memories where CORT can enhance new emotionally arousing memories. When CORT secretion is dysregulated, anxiety-related disorders can develop. The present study aimed to determine whether metyrapone, a CORT synthesis inhibitor, could diminish the fear-enhancing effects of early life stress. Rodents exposed to early life stress show subsequent stress-induced enhancement of fear learning (SEFL). Infant mice were administered metyrapone or vehicle prior to stress exposure. Stress exposure consisted of 15 footshocks in Context A, while non-stressed control mice received zero footshocks. The next day, mice were tested in Context A to determine their fear memory for the stress context. The following day, mice were placed into a novel context (B) where they received 1-footshock fear conditioning. Finally, the mice were tested the next day for their fear memory of the fear conditioning context (B). We did not observe SEFL in these mice. We believe that this is a result of maternal buffering of the stress exposure. Therefore, we were not able to assess whether metyrapone blocked SEFL. However, we are concerned about the use of metyrapone moving forward, as this drug produced sedative effects that were observed during the stress exposure session. Future studies addressing a role for CORT in mediating the induction of long-term stress effects should be approached by targeting other mechanisms of CORT signaling or other compounds that do not produce sedation. This study is relevant to my intended career as a clinical psychologist because I plan to work with children who have been exposed to trauma and, thus, it is important to understand the neurobiological mechanisms of stress.
Authors: Elle Henley, Manuel Acuna, Kate Brand, Amanda Reichert, Dr. Jennifer Quinn
Faculty Advisor: Dr. Jennifer Quinn, Psychology
Graduate Student Advisor: Amanda Reichert
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