Elsevier

Experimental Neurology

Volume 270, August 2015, Pages 72-77
Experimental Neurology

The influence of the cage environment on rodent physiology and behavior: Implications for reproducibility of pre-clinical rodent research

https://doi.org/10.1016/j.expneurol.2015.04.010Get rights and content

Highlights

  • A clearly defined stable environment is essential to generating consistent experimental outcomes.

  • The purpose of this article is to help investigators gain a better understanding of how even seemingly minor environmental changes on the animals and the data.

  • The cage environment is highly complex; the perceptions and experiences of cage occupants may not conform to human assumptions.

  • A complete and detailed description of the animal environment is a vital part of any research methods section.

Abstract

The reproducibility of pre-clinical research is an important concern that is now being voiced by constituencies that include the National Institutes of Health, the pharmaceutical industry, Congress, the public and the scientific community. An important facet of performing and publishing well-controlled reproducible pre-clinical research is to stabilize and more completely define the environment of the animal subjects. Scientists who use rodents in research generally recognize the importance of maintaining a stable animal environment. However, despite a theoretical and general awareness of these issues, many may lack a true appreciation of how significantly even seemingly minor variations in the environment can affect research outcomes. The purpose of this article is to help investigators gain a more comprehensive and substantiated understanding of the potentially significant impact of even seemingly minor environmental changes on the animals and the data. An important caveat to this article is that the examples presented were selected from a very large literature, admittedly in order to illustrate certain points. The goal of this article is not to provide an overview of the entire literature on how the environment affects rodents but rather to make preclinical scientists more aware of how these factors can potentially influence the experimental data and contribute to poor reproducibility of research.

Section snippets

Caging

The rodent cage, also called the primary enclosure, comes in many varieties (e.g., open top and closed top, ventilated or non-ventilated) and can vary in terms of size, bedding, enrichment devices, and other attributes. Even the position of the cage on the rack can influence the outcome of behavioral tests (Izidio et al., 2005). Another attribute that is rarely considered is the color of the cage. This fundamental feature of the environment was recently shown to significantly influence the

Noise

Noise is another environmental variable that can have a significant uncontrolled impact on laboratory animals and potentially reduce replicability both within and among laboratories. Exposure to various environmental sounds can lead to changes in multiple organ systems, making what laboratory animals hear of consequence for researchers beyond those solely interested in hearing (Turner et al., 2005). Strain and species differences in hearing can potentially contribute to non-reproducible

Social housing

Another common variant in how rodents are maintained is housing density. For some studies, individual housing is preferred or necessary, whereas in other cases, rodents may be housed in groups that vary in number and density as a function of caging type, duration of the study, purpose of the study, and other factors. Furthermore, an important fact to recognize is that all mice housed in the same cage are not necessarily identical, even if highly inbred. Differences among cage mates may be

Animal management and manipulation

Specific facets of how rodents are managed, handled, or used experimentally can also influence research outcomes. Even whether the animal is awake or asleep when removed from the cage for testing can influence some test results (Izidio et al., 2005). For example changing rodent cages is an essential component of animal care. However, this disruption in the animal environment is likely to alter animal physiology and behavior for some period of time after the event. To quantify this time period,

Environmental enrichment

Cage environments also often differ across laboratories and even within laboratories due to the use, often undocumented and unreported, of environmental enrichment (EE). Some research is designed to specifically test the impact of an enriched environment on the development or resolution of disease (e.g., models of Parkinson's disease, traumatic brain injury, myasthenia gravis). However, in many cases, environmental enrichment (EE) is provided in an effort to improve the well-being of the

Summary and conclusions

One of the major advantages of using rodents as models in preclinical research is the ability to control all aspects of their environment, as is clearly impossible in people. The examples presented show that a wide variety of environmental influences can contribute to problems with reproducibility of research results using rodents. Controlling these influences can be difficult. For example, despite careful attention to standardizing laboratory environment, animal maintenance and test

Acknowledgment

This work was supported by the Southern Illinois University School of Medicine.

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