Profiling of research domain criteria-based behaviors following single prolonged stress in male C57BL/6J mice.

Abstract

Post-traumatic stress disorder (PTSD) affects approximately one in 11 people throughout their lifetime yet current treatment options, such as behavioral therapies or pharmaceuticals, suffer from low medical adherence and often fail to fully address all the symptoms. Therefore, it is necessary to better understand maladaptive behaviors in PTSD to guide new treatments. Single-prolonged stress (SPS) is a rodent model of stress that parallels certain human neurophysiological and neurobehavioral changes occurring in PTSD. SPS is a single-day sequential stressor exposure-restraint stress, group forced swim, predator odor exposure, and isoflurane until loss of consciousness-followed by 7 days of stress incubation. Here, we investigated multiple cohorts of male C57BL/6J mice early after SPS and stress incubation (8-10 days) on behavioral tasks (elevated plus maze (EPM), three-chamber sociability, cost-benefit conflict (CBC), home cage behavior, scent avoidance and defensive burying tasks) that test multiple PTSD-related symptoms. Behavioral assessment included efforts to replicate published findings (i.e., EPM) and introducing newer tasks (i.e., CBC) that have not yet been tested in the SPS mouse model. While most of these tasks and standardized metrics failed to capture behavioral differences in SPS-treated male C57BL/6J mice, we did observe deficits in social novelty preference in the stressed mice. These studies add to a growing literature on inconsistencies in behavioral outcomes produced by the mouse SPS paradigm that could be potentially explained by mouse strain or procedural differences. Overall, this study demonstrated that behavior in male C57BL/6J mice were not affected after SPS apart from social novelty preference.