The Contribution of Environmental Enrichment to Phenotypic Variation in Mice and Rats.
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Abstract
The reproducibility and translation of neuroscience research is assumed to be undermined by introducing environmental complexity and heterogeneity. Rearing laboratory animals with minimal (if any) environmental stimulation is thought to control for biological variability but may not adequately test the robustness of our animal models. Standard laboratory housing is associated with reduced demonstrations of species typical behaviors and changes in neurophysiology that may impact the translation of research results. Modest increases in environmental enrichment (EE) mitigate against insults used to induce animal models of disease, directly calling into question the translatability of our work. This may in part underlie the disconnect between preclinical and clinical research findings. Enhancing environmental stimulation for our model organisms promotes ethological natural behaviors but may simultaneously increase phenotypic trait variability. To test this assumption, we conducted a systematic review and evaluated coefficients of variation (CVs) between EE and standard housed mice and rats. Given findings of suboptimal reporting of animal laboratory housing conditions, we also developed a methodological reporting table for enrichment use in neuroscience research. Our data show that animals housed in EE were not more variable than those in standard housing. Therefore, environmental heterogeneity introduced into the laboratory, in the form of enrichment, does not compromise data integrity. Overall, human life is complicated, and by embracing such nuanced complexity into our laboratories, we may paradoxically improve on the rigor and reproducibility of our research.
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The use of manipulations to enhance positive welfare in laboratory animals has been shown not to be a source of variability.
“The use of manipulations to enhance positive welfare in laboratory animals has been shown not to be a source of variability ( Kentner et al., 2021), and a possible contribution towards improved model validity and data reproducibility ( Loss et al., 2021; Van De Weerd et al., 2004; Würbel & Garner, 2007).”
From Stage 2 Registered Report: Refinement of tickling protocols to improve positive animal welfare in laboratory rats (2025) · cites this paper as Kentner et al., 2021
The Results report that environmental enrichment did not generally make mice and rats more variable than controls. The claim extends that finding to welfare-enhancing manipulations in laboratory animals generally; the Discussion also notes increased variability on some measures in naïve male enriched rats. (LLM, conf=0.84)
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Environmental Enrichment for Rats and Mice Housed in Laboratories: A Metareview
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What is ‘natural’ about naturalistic neuroscience?
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“7,11,12 Overall, an understanding of the effects of different housing scenarios is essential in guiding future protocols and standards for the improvement of laboratory animal welfare as well as potentially detecting more subtle experimental differences.”
Parallel Animal-Centered Ethics
Peacock, J., Brey, L., & Levinson, L. (2025) · International Conference on Animal-Computer Interaction (ACI) · doi:10.1145/3768539.3768557
“Reviews and articles on the welfare and housing of laboratory rats and mice highlight an increasing recognition that there is a need to adopt approaches with laboratory animals that promote a greater quality of life [39, 52, 53].”
Animal models in psychedelic research – Tripping over translationPreprint
Hay, M. Y. A. E., Cukić, A., Schölvinck, M. L., & Havenith, M. N. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.14.699469
Of mice and gender: considering gender norms in rodent models
Engel, L., Einstein, G., & Rozeske, R. R. (2026) · Biology of Sex Differences · doi:10.1186/s13293-026-00909-6
“However, enrichment type and quantity varies widely across labs, potentially contributing to variable experimental results [54].”
Estrázulas, M., Neculqueo, G. W., Farias, A. B. S., & Campos, M. M. (2026) · British Journal of Pharmacology · doi:10.1111/bph.70571
Mohammed, A., Kaur, T., Panwar, P., Ghosh, S., Ahmad, H., Kumbhakar, S., Müftüoğlu, M., Viscomi, C. F., & Sengupta, S. (2026) · EMBO Molecular Medicine · doi:10.1038/s44321-026-00532-3
- Authors
- Kentner, A. C., Speno, A. V., Doucette, J., & Roderick, R. C.
- Affiliations
- Massachusetts College of Pharmacy and Health Sciences (US)
- Corresponding author
- Kentner, Amanda C.
- Venue
- eneuro
- Publisher
- Society for Neuroscience
- Published
- 2021-02-23
- Volume
- 8
- Issue
- 2
- Pages
- ENEURO.0539-20.2021
- ISSN
- 2373-2822 (ISSN-L)
- PMC
- PMC7986535
- OpenAlex
- W3130699649
- Semantic Scholar
- 83bc95e4779b1802b907f13215f643dfe6d0838f
- Cited by
- 37
- References
- 38
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 4 · 2023: 4 · 2022: 11 · 2021: 3
- FWCI
- 6.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- eNeuro (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Mental Health (R15MH114035)
- MCPHS Summer Undergraduate Research Fellowship
- Topics
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Health Sciences › Veterinary › Small Animals › Animal Behavior and Welfare Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- environmental enrichment, phenotypic variability, coefficient of variation, laboratory animal housing, mice, rats, translational neuroscience, reproducibility, animal models of disease
- MeSH terms
- Biological Variation, Population, Animals, Behavior, Animal, Housing, Animal, Reproducibility of Results, Mice, Rats
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