The Contribution of Environmental Enrichment to Phenotypic Variation in Mice and Rats

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.

Environmental Enrichment for Rats and Mice Housed in Laboratories: A Metareview

“…Approximately 70% of enrichment studies from 1985 to 2004 focused on laboratory animals, especially rodents. Publications on this topic appeared in the literature with increasing frequency from 1999 onward, related to growing interest from neuroscientists [ 45 ], and this trend has continued to date [ 46 ]. A PubMed search for “environmental enrichment” and “rats” or “mice” identified 662 publications from 2020 alone.…”

Evaluation of different types of enrichment - their usage and effect on home cage behavior in female mice

“…Studies with rats have also shown a major influence of housing conditions on the affective state and cognitive bias, thus also the emotional well-being of laboratory animals [ 21 ]. In the context of the reproducibility crisis, it is worth noting that concerns that enrichment in general increases the variation in experimental results have not been confirmed [ 10 , 20 , 22 – 25 ].…”

Maternal immune activation accelerates puberty initiation and alters mechanical allodynia in male and female C57BL6/J mice

“…This seems contrary to the general beneficial effects of EE. One possible explanation is sex differences in the response to EE, which has not been well studied in previous EE research which has tended to focus on males (Kentner et al, 2019b;Kentner et al, 2021). Of the work that has explored sex-differences, some studies in rats found an overall greater effects of EE for males than for females, in terms of locomotor activity (Elliott and Grunberg, 2005), social exploration (Peña et al, 2006), and social memory.…”