Elsevier

Journal of Neuroscience Methods

Volume 234, 30 August 2014, Pages 139-146
Journal of Neuroscience Methods

Basic Neuroscience
Burrowing and nest building behavior as indicators of well-being in mice

https://doi.org/10.1016/j.jneumeth.2014.02.001Get rights and content

Highlights

  • Nest building and burrowing are spontaneous home cage behaviors of mice.

  • Both behaviors reflect easy-to-quantify activities of daily living.

  • Reduction of performance correlates with a variety of detrimental states in mice.

  • Nest building and burrowing may be sensitive tools to assess animal well-being.

Abstract

The assessment of pain, distress and suffering, as well as evaluation of the efficacy of stress-reduction strategies, is crucial in animal experimentation but can be challenging in laboratory mice. Nest building and burrowing performance, observed in the home cage, have proved to be valuable and easy-to-use tools to assess brain damage or malfunction as well as neurodegenerative diseases. Both behaviors are used as parameters in models of psychiatric disorders or to monitor sickness behavior following infection. Their use has been proposed in more realistic and clinically relevant preclinical models of disease, and reduction of these behaviors seems to be especially useful as an early sign of dysfunction and to monitor disease progression. Finally, both behaviors are reduced by pain and stress. Therefore, in combination with specific disease markers, changes in nest building and burrowing performance may help provide a global picture of a mouse's state, and thus aid monitoring to ensure well-being in animal experimentation.

Introduction

Most countries have regulations for the breeding, housing and use of animals for scientific experimentation that aim to ensure laboratory animal well-being. These regulations emphasize the importance of reducing pain, distress and suffering by choosing refined breeding, housing and experimental procedures, and the importance of anesthetic and analgesic protocols for animals possibly experiencing pain, distress or suffering. In particular, they highlight the significance of the assessment and quantification of pain, distress and suffering, as well as evaluation of the efficacy of pain-, distress- and suffering-reduction strategies (see, for example, Directive 2010/63/EU). In addition, in many countries, including the countries of the European Union and Switzerland, it is mandatory to grade, prospectively and retrospectively, the level of discomfort and harm inflicted by experiment (Bundesamt für Veterinärwesen, 1994, Bundesamt für Veterinärwesen, 1995, The European Parliament and the Council of the European Union, 2010). The essential prerequisite of these practices is the reliable assessment of well-being or its deterioration in laboratory animals.

However, factors that determine well-being in mice – the most widely used laboratory species (Baumanns, 2004) – remain poorly understood (Clark et al., 1997) and hints of reduced well-being in these animals may be subtle (Peterson, 2004, Stasiak et al., 2003, van Sluyters and Obernier, 2004). Obvious clinical signs of reduced well-being in mice, such as sunken flanks, neglected grooming or piloerection, are evidence of a severely impaired, often moribund, health status in mice (FELASA, 1994). Diseases or interventions with a lesser impact seem not to evoke such clearly recognizable changes (Dawkins, 1980, Jirkof et al., 2010, Stasiak et al., 2003).

Behaviors that can be observed easily in a non-invasive manner might provide more sensitive cues as to the internal state of an animal compared to classical clinical monitoring tools. Observations in the home cage are especially advantageous as they impose minimal stress on the animal and reduce unwanted effects such as novelty stress, stress-induced analgesia or other changes in physiology and behavior that may be caused by the unfamiliar environment of a test apparatus. Recent studies have demonstrated the potential and promising use of complex behavioral indicators in the assessment of pain, distress and suffering in the laboratory mouse in veterinary research (Arras et al., 2007, Jirkof et al., 2010, Langford et al., 2010, Roughan et al., 2009) as well as in preclinical research (Deacon, 2006b, Deacon, 2006c), but there remains a need to monitor species-typical behaviors in order to fully explore the underlying principles of murine disease and pain models, and to demonstrate the therapeutic effects of treatments (Blackburn-Munro, 2004, Mogil, 2009, Sano et al., 2009).

The assessment of pain- or distress-evoked aberrant behaviors or facial expressions (Langford et al., 2010, Roughan et al., 2009, Wright-Williams et al., 2007) has proved a sensitive approach toward a more clinically relevant estimation of well-being in mice.

As well as observing aberrant behaviors and signs of reduced well-being, indicators of positive well-being can also be assessed (Arras et al., 2007, Boissy et al., 2007, Jirkof et al., 2010). The display of behavioral diversity and so-called “luxury” behaviors or other highly motivated but, at least in the laboratory, non-essential behaviors, indicates that important needs of the animal are being met, and can serve as a sign of well-being. These kinds of behaviors are normally the first to be reduced in challenging situations (Boissy et al., 2007) and their absence might therefore indicate decreased well-being. These natural, spontaneous and often complex home cage behaviors may mirror activities of daily living (ADL) in humans that are affected by many clinical conditions, including chronic pain – a factor known to have an essential impact on quality of life in human patients (Lau et al., 2013, Torres-Lista and Gimenez-Llort, 2013, Urban et al., 2011).

Nest building (also described as nesting) and burrowing are spontaneous behaviors that have been proposed to represent such ADL in mice (Deacon, 2012), and good performance in these home cage behaviors might be indicative of normal behavioral function or well-being in mice and rats (Arras et al., 2007, Deacon, 2012, Huang et al., 2013, Jirkof et al., 2010, Jirkof et al., 2013b, Van Loo et al., 2007). This article reviews data on nest building and burrowing behavior from basic research and applied animal welfare research that may give hints as to the feasibility of using these behaviors for monitoring well-being in laboratory mice.

Section snippets

Nest building in laboratory mice

The construction of nests is common in rodent species. Wild house mice build nests to provide heat conservation, shelter from elements, predators, and competitors and to allow successful reproduction (Deacon, 2006b, Hess et al., 2008, Latham and Mason, 2004). Nest building increases lifetime reproductive success and is an essential thermoregulatory adaption (Berry, 1970, Bult and Lynch, 1997).

The motivation and ability to perform the behavioral sequence culminating in a finished nest persists

Discussion

Nest building and burrowing performance have proved valuable tools with which to assess brain damage or malfunction as well as the progression of neurodegenerative diseases. These behaviors are also used in models of psychiatric disorders or to monitor sickness behavior, and have been proposed for use in more realistic and clinically relevant preclinical models of disease. They seem especially useful as early signs of beginning dysfunction and for the monitoring of disease progression, and

Conclusions

Nest building and burrowing behavior are likely to represent ADL in laboratory mice that are impaired by pain, stress, infection and in several psychiatric and neurodegenerative murine disease models. With few exceptions this impairment is not due to motor deficits or reduced overall activity per se. As all of these states are known to decrease quality of life in human patients, and are assumed to do so also in animals, both behaviors offer a sensitive and easy to use tool with which to assess

Acknowledgment

This work was sponsored by grants from the Federal veterinary office (Bern, Switzerland).

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