{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:38:37Z","timestamp":1788514717859,"version":"build-2803163510"},"reference-count":202,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["CIMB"],"abstract":"<jats:p>The purpose of this article is to examine a previously unrecognized role for the vasopressin\u2013oxytocin (VP-OT) system in mammalian \u201cstress-response hormesis.\u201d The current review adds hormesis to the long list of beneficial effects of OT. Hormesis, a biphasic adaptive response to low-level stressors, is introduced here to contextualize the dynamic roles of oxytocin and vasopressin. As with hormesis, the properties of the VP-OT system are context-, time-, and dose-sensitive. Here we suggest that one key to understanding hormesis is the fact that VP and OT and their receptors function as an integrated system. The VP-OT system is capable of changing and adapting to challenges over time, including challenges necessary for survival, reproduction and sociality. Prior research suggests that many beneficial effects of OT are most apparent only following stressful experiences, possibly reflecting interactions with VP, its receptors and other components of the hypothalamic\u2013pituitary\u2013adrenal axis. The release of OT is documented following various kinds of hormetic experiences such as birth, vigorous exercise, ischemic events and the ingestion of emetics, including psychedelics. The phasic or cyclic modulation of VP and related \u201cstress\u201d hormones, accompanied or followed by the release of OT, creates conditions that conform to the core principles of hormesis. This concept is reviewed here in the context of other hormones including corticotropin releasing hormone (CRH) and urocortin, as well as cytokines. In general, VP and classic \u201cstress hormones\u201d support an active response, helping to quickly mobilize body systems. OT interacts with all of these, and may subsequently re-establish homeostasis and precondition the organism to deal with future stressors. However, the individual history of an organism, including epigenetic modifications of classical stress hormones such as VP, can moderate the effects of OT. Oxytocin\u2019s effects also help to explain the important role of sociality in mammalian resilience and longevity. A hormetic perspective, focusing on a dynamic VP-OT system, offers new insights into emotional and physical disorders, especially those associated with the management of chronic stress, and helps us to understand the healing power of social behavior and perceived safety.<\/jats:p>","DOI":"10.3390\/cimb47080632","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T09:56:42Z","timestamp":1754647002000},"page":"632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Oxytocin, Vasopressin and Stress: A Hormetic Perspective"],"prefix":"10.3390","volume":"47","author":[{"given":"Hans P.","family":"Nazarloo","sequence":"first","affiliation":[{"name":"Department of Psychiatry, College of Medicine-Jacksonville, University of Florida, 580 West 8th St., Tower II, 6th Floor, Jacksonville, FL 32209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcy A.","family":"Kingsbury","sequence":"additional","affiliation":[{"name":"Lurie Center for Autism, Mass General Research Institute, Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Lamont","sequence":"additional","affiliation":[{"name":"Lurie Center for Autism, Mass General Research Institute, Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin V.","family":"Dale","sequence":"additional","affiliation":[{"name":"Dedman College of Humanities and Sciences, Southern Methodist University, Dallas, TX 75205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parmida","family":"Nazarloo","sequence":"additional","affiliation":[{"name":"Traumatic Stress Research Consortium, Kinsey Institute, Indiana University, Bloomington, IN 47405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3963-1654","authenticated-orcid":false,"given":"John M.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Porges","sequence":"additional","affiliation":[{"name":"Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville, FL 32611, USA"},{"name":"Center for Cognitive Aging and Memory, Evelyn F. and William L. 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Sue","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, College of Medicine-Jacksonville, University of Florida, 580 West 8th St., Tower II, 6th Floor, Jacksonville, FL 32209, USA"},{"name":"Traumatic Stress Research Consortium, Kinsey Institute, Indiana University, Bloomington, IN 47405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102588","DOI":"10.1016\/j.arr.2024.102588","article-title":"The Catabolic\u2013Anabolic Cycling Hormesis Model of Health and Resilience","volume":"102","author":"Calabrese","year":"2024","journal-title":"Ageing Res. 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