Animal models with construct validity for studying epigenetic processes in neurobehavior

Many ethical and technical challenges hinder exploration of molecular mechanisms, including epigenetic processes underlying neuropsychiatric disorders in humans. Therefore, there is a need for animal models for such disorders that will allow a better understanding of disease mechanisms. Here, we explore the use of animal models with construct validity for such disorders. The chapter emphasizes the importance of construct validity of the models and highlights key considerations, including the temporal dynamics of disorders, relevant tissues and brain regions, and the need for genetic and environmental components of the model to align with the human pathophysiology. We review several of the most established models for major neuropsychiatric disorders such as anxiety, depression, posttraumatic stress disorder, and substance use disorder. We describe why models such as the Chronic Social Defeat Stress model, which closely replicates the types of social stressors that are known to contribute to depression; the drug self-administration model, which captures the motivational processes underlying substance use disorder; or the Predator Scent Stress model, which uses ecologically relevant stimuli that mimic the types of psychologic threat and traumatic experiences implicated in human posttraumatic stress disorder, are important. We discuss models that have construct validity and provide examples and use cases for these models in studies that explored the epigenetic mechanisms of neuropsychiatric disorders. Overall, this chapter underscores the importance of choosing a valid animal model for research to allow for a better understanding of the underlying epigenetic mechanisms of neuropsychiatric disorders.