A Protocol for the Induction of Posttraumatic Stress-Disorder (PTSD)-like Behavior in Mice

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that precipitates in ~10% of individuals exposed to a traumatic event (TE). Symptoms include recurrent and intrusive thoughts, sleep disturbance, hypervigilance, exaggerated startle, and reckless or destructive behavior. Given the complex and heterogeneous nature of the disease, animal models for PTSD-like symptomatology are of increasing interest to the field of PTSD research. Because resilience to PTSD-like symptomatology is an important epidemiologic aspect of PTSD, animal models that resolve vulnerable and resilient animals are of particular value. Due to the complex nature of the PTSD phenotype and the potential overlaps between PTSD-like behavior and behaviors associated with other stress-induced psychopathologies such as anxiety or depression, animal models that utilize multiple readouts for PTSD-like behavior are also of increasing value. We utilize a paradigm developed by Lebow et al. 2012 for the induction and identification of PTSD-like symptomatology in mice. This paradigm utilizes inescapable electric foot shock, administered in two decontextualized sessions over two consecutive days. Stressed mice perform four behavioral tests-dark/light transfer, marble burying, acoustic startle, and home cage activity-to generate five behavioral readouts of PTSD-like behavior: % risk assessment (%RA), % marbles buried (%MB), % prepulse inhibition (%PPI), latency to peak startle amplitude (LPSA), and % light phase activity (%LPA). PTSD-like symptomatology is characterized by decreased %RA, increased %MB, decreased %PPI, decreased LPSA, and increased %LPA. The 20% of animals displaying the most PTSD-like behavior in each test are awarded a certain number of points depending on the test, and animals scoring sufficient points are designated as PTSD-like, while animals scoring no points are designated PTSD-resilient. This paradigm identifies PTSD-like behavior in ~15% of animals, a rate comparable to that observed in humans. This protocol represents a robust and reproducible paradigm for the induction of PTSD-like behavior in mice.