The Stress Response Is Adaptive in a Context- and State-Dependent Manner

A long-standing question in stress physiology is when and how the adaptive stress response can become maladaptive. In this narrative review primarily focusing on experimental studies in (male) animals, we argue that this is not merely a semantic matter but that—within limits—the organism’s response to an acute or chronic stressor and the interpretation thereof as adaptive or maladaptive very much depends on the context and the circumstances under which the response is studied, including the task configuration and the state of the organism, in relation to its recent and past stress history. We substantiate this by providing examples at the behavioral level. The behavioral findings can be understood from neurophysiological studies, which show that the recent and distant (stress) history of an organism shapes its brain function and plasticity. Consequently, renewed exposure to a challenging situation evokes a different cellular and circuit response than it would without this history, pointing to metaplastic changes. Overall, we argue that many of the stress-induced effects that are currently interpreted as maladaptive are, in fact, adaptive as long as the environment aligns with the circumstances predicted by the individual’s experience. Adaptation to novel circumstances will require (behavioral) flexibility. Understanding the relationship between metaplastic or state-dependent cellular responses on the one hand and flexible behavioral outcomes that foster adaptation on the other hand may contribute to developing interventions or preventing stress-related mental disorders.