A behavioral screening method for predicting PTSD-like phenotypes: Novel application to female rats

Abstract

Background

Only a small percentage of trauma-exposed subjects develop PTSD, with females being twice as likely. Most rodent models focus on males and fail to account for inter-individual variability in females.

New method

We tested a behavioral PTSD model in female rats to distinguish between susceptible and resilient individuals. In Experiment 1, female rats underwent footshocks paired with social isolation, a PTSD risk factor. They were re-exposed to the conditioned context to test memory retention, and assessed in the Elevated Plus Maze (EPM) and Social Interaction (SI) tests for anxiety and social behavior.

Results

Footshock-exposed rats showed fear memory retention up to 16 days, indicated by elevated freezing behavior during re-exposure. They also exhibited reduced exploration in the EPM and less SI time compared to controls. In Experiment 2, we classified rats into normal responders, susceptible, and resilient groups based on locomotor activity after trauma, correlating with memory retention and anxiety.

Comparison with existing methods

Unlike existing models focused on males and lacking predictive variables before trauma, our method identifies PTSD-like susceptibility and resilience in female rats by using exploratory behavior as a predictor before trauma exposure.

Conclusions

Exploratory activity in a novel environment after trauma and before extinction is a reliable predictor of PTSD-like phenotypes and differentiates between susceptible and resilient female rats.