Animal models of PTSD: a challenge to be met

Abstract

Recent years have seen increased interest in psychopathologies related to trauma exposure. Specifically, there has been a growing awareness to posttraumatic stress disorder (PTSD) in part due to terrorism, climate change-associated natural disasters, the global refugee crisis, and increased violence in overpopulated urban areas. However, notwithstanding the increased awareness to the disorder, the increasing number of patients, and the devastating impact on the lives of patients and their families, the efficacy of available treatments remains limited and highly unsatisfactory. A major scientific effort is therefore devoted to unravel the neural mechanisms underlying PTSD with the aim of paving the way to developing novel or improved treatment approaches and drugs to treat PTSD. One of the major scientific tools used to gain insight into understanding physiological and neuronal mechanisms underlying diseases and for treatment development is the use of animal models of human diseases. While much progress has been made using these models in understanding mechanisms of conditioned fear and fear memory, the gained knowledge has not yet led to better treatment options for PTSD patients. This poor translational outcome has already led some scientists and pharmaceutical companies, who do not in general hold opinions against animal models, to propose that those models should be abandoned. Here, we critically examine aspects of animal models of PTSD that may have contributed to the relative lack of translatability, including the focus on the exposure to trauma, overlooking individual and sex differences, and the contribution of risk factors. Based on findings from recent years, we propose research-based modifications that we believe are required in order to overcome some of the shortcomings of previous practice. These modifications include the usage of animal models of PTSD which incorporate risk factors and of the behavioral profiling analysis of individuals in a sample. These modifications are aimed to address factors such as individual predisposition and resilience, thus taking into consideration the fact that only a fraction of individuals exposed to trauma develop PTSD. We suggest that with an appropriate shift of practice, animal models are not only a valuable tool to enhance our understanding of fear and memory processes, but could serve as effective platforms for understanding PTSD, for PTSD drug development and drug testing.