Adaptation of the hypothalamus-pituitary-adrenal axis to daily repeated stress does not follow the rules of habituation: A new perspective

• Published in: Neuroscience and biobehavioral reviews Vol. 56; pp. 35 - 49
• Main Authors: Rabasa, Cristina, Gagliano, Humberto, Pastor-Ciurana, Jordi, Fuentes, Silvia, Belda, Xavier, Nadal, Roser, Armario, Antonio
• Format: Journal Article
• Language: English
• Published: United States 01.09.2015
• Subjects: Adaptation, Physiological - physiology; Animals; Habituation, Psychophysiologic; Humans; Hypothalamo-Hypophyseal System - physiopathology; Pituitary-Adrenal System - physiopathology; Stress, Psychological - pathology; Stress, Psychological - physiopathology; Stress, Psychological - psychology; Corticosterone; ACTH; Immobilization; Repeated stress; Restraint; c-fos; Water stress; Habituation
• ISSN: 0149-7634; 1873-7528
• DOI: 10.1016/j.neubiorev.2015.06.013

Repeated exposure to a wide range of stressors differing in nature and intensity results in a reduced response of prototypical stress markers (i.e. plasma levels of ACTH and adrenaline) after an acute challenge with the same (homotypic) stressor. This reduction has been considered to be a habituation-like phenomenon. However, direct experimental evidence for this assumption is scarce. In the present work we demonstrate in adult male rats that adaptation of the hypothalamus-pituitary-adrenal (HPA) axis to repeated stress does not follow some of the critical rules of habituation. Briefly, adaptation was stronger and faster with more severe stressors, maximally observed even with a single exposure to severe stressors, extremely long-lasting, negatively related to the interval between the exposures and positively related to the length of daily exposure. We offer a new theoretical view to explain adaptation to daily repeated stress.