Development of an Animal Model of Military-Relevant Traumatic Stress.

Abstract

Acute Stress Reactions (ASRs) affect a subgroup of individuals who experience traumatic stress. In the context of military operations, such reactions are often termed Combat and Operational Stress Reactions (COSRs). COSRs not only encompass all symptoms of ASRs but also include additional symptoms related to military combat and may develop at a rate higher than the general public experiences ASRs. Despite an obvious need, there are currently no approved pharmacologic treatments or guidelines for ASR and/or COSR. Preclinical rodent stress models and behavioral assessments are used to evaluate pharmacotherapies and elucidate underlying mechanisms. Here, we combined established traumatic stress models to develop a model of traumatic stress relevant to military trauma exposure and measured behavioral outcomes that reflect outcomes observed in ASRs and COSRs. Adult male rats underwent exposure to either a combination of two or three traumatic stress exposures (e.g., predator exposure, underwater trauma (UWT), and/or inescapable shock) or control procedures. Behavioral performance on the open field, elevated plus maze, and acoustic startle response (SR) was then assessed 24- and 48-hours following stress/control procedures. In Experiment 1, rats were exposed to a two-stressor model, where predator exposure was coupled with UWT. Minor behavioral deficits were observed in SR for stress-exposed rats as compared to controls. In Experiment 2, inescapable shock was added to predator exposure and UWT. Behavioral performance deficits were observed across all behavioral tests. In Experiment 3, procedures from Experiment 2 were repeated with the only major modification being a shortened predator exposure duration, which resulted in performance deficits in SR only. We found that the three-stressor model of Experiment 2 resulted in the greatest overall behavioral disturbance (both in the number of variables and magnitude of stress effects). Interestingly, behavioral deficits elicited from the shorter predator exposure were distinct from those observed with longer predator exposure times. Together, these results generally suggest that combined preclinical stressors with military-relevant elements result in behavioral performance deficits reflective of post-trauma phenotypes in Soldiers. The present findings support the use of both physical and psychological stressors to model operationally relevant traumatic stress exposure.