8663 Sex differences in delayed fear incubation in mice

Abstract

Abstract Disclosure: M. Littlepage-Saunders: None. M. Rusnak: None. M. Tsuda: None. T. Wu: None. Post-traumatic stress disorder (PTSD) has a lifetime prevalence of 1 in 13 people. It is not fully understood why some are more vulnerable to developing PTSD whereas others are more resilient. Among those who develop PTSD, about a quarter have delayed-onset PTSD where onset of symptoms occur at 6 months or later after experiencing a traumatic event. While there is recognition of this type of PTSD, the underlying mechanism is poorly understood. The development of PTSD is more prevalent in women than men. However, previous preclinical and clinical studies have focused mainly on males. Thus, there lacks an understanding of this sex difference. To enhance our understanding of the causal mechanisms, we designed a study with mice to compare the effect of sex on delayed fear incubation. We expected the female mice to show increased fear responses that would suggest more chronic delayed fear incubation than the male mice. To test this, we evaluated distance travelled, freezing, and latency until the first freezing episode in adult male and female C57Bl/6J mice (7-8 weeks of age; n=8/group) using a delayed fear incubation behavioral assay. Animals were placed in a fear conditioning chamber for a 198 s acclimation period and then administered a single 2 s scrambled footshock of 1.5 mA via the metal grid floor. After an additional 60 s, animals were returned to their home cage. At specific time after shock application, animals underwent a fear recall test where the animals were placed back in the shock chamber for a total of 180 s without any additional footshocks and then returned to their home cage. The study was based on a 2X2 factorial design comprising of sex (male vs female) and recall time (1 day and 14 days post shock). The data showed an increasing freezing trend (p=0.08) at d 14 compared to their recall d 1 counterparts. There was no effect of time or sex on distance travelled or latency until the first freezing episode. Interestingly, female mice showed less freezing when compared to the male mice. Ongoing experiments will look more into circuitry-level changes by comparing neuronal activation through cFos expression in different brain regions that are a part of the limbic system and/or have been associated with fear: the amygdala, hippocampus, prefrontal cortex, and paraventricular nucleus. Presentation: 6/2/2024