The DOI matches its Crossref record; 193 of the 193 references it cites were found in a registry or an index.
Inoculation stress hypothesis of environmental enrichment.
Open accessAbstract
One hallmark of psychiatric conditions is the vast continuum of individual differences in susceptibility vs. resilience resulting from the interaction of genetic and environmental factors. The environmental enrichment paradigm is an animal model that is useful for studying a range of psychiatric conditions, including protective phenotypes in addiction and depression models. The major question is how environmental enrichment, a non-drug and non-surgical manipulation, can produce such robust individual differences in such a wide range of behaviors. This paper draws from a variety of published sources to outline a coherent hypothesis of inoculation stress as a factor producing the protective enrichment phenotypes. The basic tenet suggests that chronic mild stress from living in a complex environment and interacting non-aggressively with conspecifics can inoculate enriched rats against subsequent stressors and/or drugs of abuse. This paper reviews the enrichment phenotypes, mulls the fundamental nature of environmental enrichment vs. isolation, discusses the most appropriate control for environmental enrichment, and challenges the idea that cortisol/corticosterone equals stress. The intent of the inoculation stress hypothesis of environmental enrichment is to provide a scaffold with which to build testable hypotheses for the elucidation of the molecular mechanisms underlying these protective phenotypes and thus provide new therapeutic targets to treat psychiatric/neurological conditions.
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“They propose that living in a complex environment places animals in a state of chronic very mild stress that inoculates against subsequent stressors.”
From Effects of Maternal Deprivation and Complex Housing on Rat Social Behavior in Adolescence and Adulthood (2018) · cites this paper as Crofton et al., 2015
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An adverse early life environment can enhance stress resilience in adulthood
Santarelli, S., Zimmermann, C. A., Kalideris, G., Lesuis, S. L., Arloth, J., Uribe, A., Dournes, C., Balsevich, G., Hartmann, J., Masana, M., et al. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.01.021 · Cited by 166
Dandi, Ε., Kalamari, A., Touloumi, O., Lagoudaki, R., Nousiopoulou, E., Simeonidou, C., Spandou, E., & Tata, D. Α. (2018) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2018.03.003 · Cited by 154
Environmental enrichment modulates the response to chronic stress in zebrafish
Marcon, M., Mocelin, R., Benvenutti, R., Costa, T., Herrmann, A. P., de Oliveira, D. L., Koakoski, G., Barcellos, L. J. G., & Piato, Â. (2018) · Journal of Experimental Biology · doi:10.1242/jeb.176735 · Cited by 133
Modelling depression in animals: at the interface of reward and stress pathways
Slattery, D. A., & Cryan, J. F. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4552-6 · Cited by 120
Oshri, A., Duprey, E. B., Kogan, S. M., Carlson, M. W., & Liu, S. (2018) · Developmental Psychology · doi:10.1037/dev0000528 · Cited by 105
Metadata
- Authors
- Crofton, E. J., Zhang, Y., & Green, T. A.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Corresponding author
- Green, Thomas A.
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 49
- Pages
- 19-31
- ISSN
- 0149-7634 (ISSN-L)
- PMC
- PMC4305384
- OpenAlex
- W2066244855
- Cited by
- 206
- References
- 193
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 17 · 2023: 21 · 2022: 21 · 2021: 15 · 2020: 24 · 2019: 18 · 2018: 27 · 2017: 21 · 2016: 17 · 2015: 4
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIDA (DA029091, DA007287)
- NINDS (NS081121)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- environmental enrichment, chronic mild stress, resilience, individual differences, addiction, depression, social interaction, isolation, cortisol, corticosterone, stress response, animal models of psychiatric disorders
- MeSH terms
- Animals, Environment, Housing, Animal, Humans, Stress, Psychological, Resilience, Psychological
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