Models of Depression for Preclinical Drug Discovery and Development: A Transitional Perspective

Animal models of depression are most frequently encountered within the pharmaceutical industry to screen molecules and detect a putative antidepressant activity of a drug. The multiplicity of approaches and models makes comprehensive statements difficult, but animal models are necessary. These are experimental arrangements where a simple system is utilized to represent a complex system. Five of the most utilized behavioral animal models of depression, the mouse Forced Swimming Test (FST), the rat FST, the Tail Suspension Test (TST), the Chronic Mild Stress (CMS) model, the Learned Helplessness (LH) paradigm, and the chronic corticosterone exposure model, are discussed in this review. All these models present various symptoms of depression in animals suggested to resemble specific aspects of human illness. Their use enables the investigation of the underlying neurobiology of depression, as well as the mechanism of action of antidepressants and the screening of potential antidepressants. Apparently, the mouse FST is the most suitable animal of depression in predicting antidepressant response as it is easily and rapidly performed, robust, specific for antidepressant drugs, and reproducible. Moreover, it permits a good correlation with clinical studies in a translational approach. In this goal, another model is presented: The chronic corticosterone exposure, a more complete neuroendocrine model that seems closer to the conditions of depression in humans. Hyperactivation of the hypothalamic-pituitary-adrenal axis (HPA axis) is one of the most described alterations in patients with depression, as well as in rodent models of pathology.