Challenges in the use of animal models and perspectives for a translational view of stress and psychopathologies

The neurobiology and development of treatments for stress-related neuropsychiatric disorders rely heavily on animal models. However, the complexity of these disorders makes it difficult to model them entirely, so only specific features of human psychopathology are emulated and these models should be used with great caution. Importantly, the effects of stress depend on multiple factors, like duration, context of exposure, and individual variability. Here we present a review on pre-clinical studies of stress-related disorders, especially those developed to model posttraumatic stress disorder, major depression, and anxiety. Animal models provide relevant evidence of the underpinnings of these disorders, as long as face, construct, and predictive validities are fulfilled. The translational challenges faced by scholars include reductionism and anthropomorphic/anthropocentric interpretation of the results instead of a more naturalistic and evolutionary understanding of animal behavior that must be overcome to offer a meaningful model. Other limitations are low statistical power of analysis, poor evaluation of individual variability, sex differences, and possible conflicting effects of stressors depending on specific windows in the lifespan. • Drug development for stress-related disorders rely heavily on animal models. • Models are used to induce phenotypes, tests are tools to assess behavioral information. • The use of animal models to study stress and psychopathology is challenging. • Animal studies unravel the complex mechanisms linking brain and behavior. • Certain human particularities are difficult or even impossible to model in animals. • To fully explore the potential of animal models translation should be done carefully