Animal models of fatigue in major depressive disorder

Fatigue is common in a host of neurological and psychiatric disorders including depression and often continues unabated even after primary symptoms of disease are treated. Its high estimated prevalence combined with the lack of effective medicines has engaged the preclinical research community to search for fatigue models. The present review briefly summarizes the most common animal models that have been brought forward along with some of the associated pharmacological validation data. Like all preclinical models, these models have issues that need to be appreciated in the generation and interpretation of data for the purposes of translation to human disease; specifically, there are deficiencies in construct validity, a lack of medicines that effectively address residual fatigue symptoms, and difficulties in defining specificity with respect to drug effects on fatigue per se. Nonetheless, existing animal models of fatigue arguably serve the valuable purpose of encouraging research in this large area of unmet medical need. Data from these models are predicted to engender human experimentation and the further development of improved model systems.