Preclinical Models of Chronic Stress: Adaptation or Pathology?

The experience of prolonged stress changes how individuals interact with their environment and process interoceptive cues, with the end goal of optimizing survival and well-being in the face of a now-hostile world. The chronic stress response includes numerous changes consistent with limiting further damage to the organism, including development of passive or active behavioral strategies and metabolic adjustments to alter energy mobilization. These changes are consistent with symptoms of pathology in humans, and as a result, chronic stress has been used as a translational model for diseases such as depression. While it is of heuristic value to understand symptoms of pathology, we argue that the chronic stress response represents a defense mechanism that is, at its core, adaptive in nature. Transition to pathology occurs only after the adaptive capacity of an organism is exhausted. We offer this perspective as a means of framing interpretations of chronic stress studies in animal models and how these data relate to adaptation as opposed to pathology.

Automated summary

The experience of prolonged stress leads to changes in how individuals interact with their environment and process interoceptive cues, aiming to optimize survival in a hostile world. The chronic stress response involves various alterations that limit further harm, including the development of behavioral strategies and metabolic adjustments. While chronic stress is often linked to pathology, we argue that it is actually an adaptive defense mechanism. Pathology occurs only when the organism's adaptive capacity is depleted. This perspective helps interpret chronic stress studies in animal models in relation to adaptation rather than pathology.