C35: The Effects of Sex and Early Life Stress on Conditioned Inhibition of Fear in Rodents

Posttraumatic stress disorder (PTSD) is a debilitating condition that occurs in a subset of individuals who experience one or more traumatic events. It is marked by recurrent memories of the traumatic event, heightened anxiety states, altered mood, and avoidance behaviors. Importantly, adverse early childhood experiences yield increased vulnerability to the development of PTSD later in life. Further, females show heightened sensitivity to PTSD occurrence. In order to address the neurobiological mechanisms that mediate PTSD, and to develop novel brain-based treatments, it is necessary to use reliable and valid animal models. Acute early life stress (aELS; 15 footshocks on postnatal day 17) is used as a rodent model of PTSD vulnerability as it promotes altered threat processing in adulthood which recapitulates important features of PTSD: enhanced fear learning, resistance to extinction, incubation of fear, and heightened anxiety. Another prominent symptom of PTSD is the overgeneralization of fear – reacting fearfully despite the presence of environmental safety cues. One approach to studying safety learning in rodents is the conditioned inhibition procedure where the animal learns that a cue predicts safety in the face of other threatening stimuli. The current study assessed whether aELS disrupts safety learning in adulthood. Given the sex disparity in PTSD diagnosis, we developed a safety learning procedure (i.e., conditioned inhibition) that is demonstrated in both male and female rats and mice, and assessed the impact of prior aELS exposure. We ran multiple pilot experiments to refine our methodology, and in our final pilot, found evidence of conditioned inhibition in both male and female mice, regardless of aELS exposure. This indicates that our current methodology is useful in future studies that wish to experiment with conditioned inhibition in both male and female rodents.

Author(s): Caroline Bartoszek, Psychology and Neuroscience Major

Advisor(s): Jennifer Quinn, Department of Psychology

Amanda Reichert, Department of Psychology