Variation in trauma-related behavioral effects using a preclinical rat model of three predator exposure stress

Abstract

The underlying mechanisms of trauma-related disorders are challenging to discover and the disorders are difficult to treat, in part due to the complex and varied expressions of response to traumatic stress. These challenges will be easier to overcome as more is understood about the variability in response to trauma. Incorporating assessment of variability into animal models of traumatic stress may allow better translation to clinical research and treatment development. In this study, we characterized variability in behavioral responses following traumatic stress exposure using a predator exposure (PE) animal model. Elevated plus maze (EPM) and acoustic startle response (SR) were used to study avoidance and arousal symptoms in male Sprague–Dawley rats. Behavioral data were compared between control (n = 31) and predator-exposed (n = 30) rats. PE behavior was clustered using k-means principal components analysis. Four clusters and three distinct subgroups were identified and were characterized as avoidant (Cluster 4, 30%), moderately avoidant (Clusters 2 and 3, 49%), and unaffected (Cluster 1, 17%). These results demonstrate that rodent responses to PE are varied, similar to human presentations following traumatic stress, suggesting it may be possible to develop treatment strategies for varied symptom presentations using a preclinical animal model.

Keywords:

• Acute stress disorder
• acute stress reaction
• post-traumatic stress disorder
• principal components analysis
• animal model
• individual differences

Acknowledgments

The authors thank present and previous lab members for laboratory assistance, Dr. Samantha Riedy for statistical assistance, and Dr. Tom Balkin for his helpful manuscript edits. The authors also thank the Veterinary Services Program of Walter Reed Army Institute of Research for their veterinary support, guidance, and animal care for the present study.

Disclaimer

Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the author and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. The research was conducted under an approved animal use protocol in an AAALAC accredited facility in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals, NRC Publication, 2011 edition.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Notes on contributors

Emily Scott MS is a data manager and bioinformatician in the Performance Assessment and Chemical Evaluation Laboratory at Walter Reed Army Institute of Research, Silver Spring, MD.

Matthew May MS is lab manager and researcher in the Performance Assessment and Chemical Evaluation Laboratory at Walter Reed Army Institute of Research, Silver Spring, MD.

Gabriella Silva BS is a researcher in the Performance Assessment and Chemical Evaluation Laboratory at Walter Reed Army Institute of Research, Silver Spring, MD.

Rachel Taylor PhD is Chief of Preclinical Operations in the Performance Assessment and Chemical Evaluation Laboratory at Walter Reed Army Institute of Research, Silver Spring, MD.

Nicole Fenlon PhD is Deputy Chief of Research Development and Integration at United States Army Medical Research Institute of Chemical Defense.

Emily Lowery-Gionta PhD is PI of the Performance Assessment and Chemical Evaluation Laboratory and Section Chief at Walter Reed Army Institute of Research, Silver Spring, MD.

Liana Matson PhD is Director of the Behavioral Biology Branch at Walter Reed Army Institute of Research, Silver Spring, MD.

Additional information

Funding

This work was supported by the Military Operational Medicine Research Program, US Army Medical Research and Development Command. The funders had no role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript.