Creating a Rat Model of Chronic Variate Stress

Abstract

Stress is a condition of human experience and an important factor in the onset of various diseases. There are numerous studies showing how stress can accelerate cell aging, immune senescence and some age-related diseases such as neurodegenerative disorders and osteoporosis. However, the effects of stress have different consequences depending on the type, duration or severity and predictability of the stressor applied. Although stress can be beneficial in its acute phase, repeated and severe stressful stimuli produce adverse effects. There are different models of stress depending on the exposure time; acute (when the stressor is applied for a short time, e.g. hours or days, and intensely) or chronic (when the stressor is applied for a long time, e.g. weeks or months, and less intensely. In these cases, the stressor can be repeated each time or different stressors can be used). The latter model is most frequently used to achieve similar conditions to those found in human diseases related to stress. Also, there are several different paradigms depending on the purpose of the study [development of drug therapies or modeling depressive behaviors; for the different paradigms see Dagnino-Subiabre, (2012)]. Here, we describe a 9-day variable-stressor paradigm with repeated and prolonged stimulation and a random daily stressor over days or weeks to minimize its predictability. This protocol has been adapted from other models of variable stress with significant modifications. The absence of predictability of the stressor applied is an important characteristic of this model compared to other models in which repeated stress is used. We avoid the use of a strong stressor, such as foot shock or tail pinch, and describe an easily reproducible new chronic mild stress model. Some models of chronic mild stress have been reported to lead to a wide range of behavioral disturbances and have been proposed as models of depression in animal studies (Cryan et al., 2005).