Refinement Database

Database on Refinement of Housing, Husbandry, Care, and Use of Animals in Research

This database, created in 2000, is updated every four months with newly published scientific articles, books, and other publications related to improving or safeguarding the welfare of animals used in research.

Tips for using the database:

  • This landing page displays all of the publications in the database.
  • Use the drop-down menus to filter these publications by Animal Type, Setting, and/or Topic.
  • Clicking on a parent category (e.g., Rodent) will include publications relating to all the items in that category (e.g., Chinchilla, Gerbil, Guinea Pig, etc.).
  • You may also add a keyword to further narrow your search.
  • Please note that at this time, only publications dated 2010 or later (with some exceptions) can be filtered by Animal Type and Topic, and only publications dated 2020 or later (with some exceptions) can be filtered by Setting. Most publications older than 2010 can only be searched by keyword. 
Swan, J., Boyer, S., Westlund, K. et al. 2023. Decreased levels of discomfort in repeatedly handled mice during experimental procedures, assessed by facial expressions. Frontiers in Behavioral Neuroscience 17, 1109886.

Mice are the most commonly used laboratory animal, yet there are limited studies which investigate the effects of repeated handling on their welfare and scientific outcomes. Furthermore, simple methods to evaluate distress in mice are...

Veness, A., Coyle, C., Murphy, S. et al. 2023. Minimising aggression in CD-1 and CD-1 background male mice with different enrichment types. Animal Technology and Welfare 22(1), 74–76.

Cage-mate aggression is a well-known problem that is more prevalent in certain strains of mice and is one of the most common reasons for single housing, increased stress levels, premature death and euthanasia. Numerous methods...

Alef, R., Blaser, R. E. 2023. Social group during housing and testing modulates the effect of ethanol on zebrafish (Danio rerio) behavior. Behavioural Processes 209, 104877.

Zebrafish (Danio rerio) are a popular model organism in behavioral pharmacology research due to many genetic and neurological similarities with humans. As a social species, the presence (or absence) of conspecifics during housing and testing...

Xu, J. J., Lucero, M. Y., Herndon, N. L. et al. 2023. Comparison of a minimally invasive transthoracic approach and a surgical method for intrapleural injection of tumor cells in mice. Comparative Medicine 73(2), 120–126.

Intrapleural injections can be used in mice to deliver therapeutic and diagnostic agents and to model human disease processes (for example, pleural fluid accumulation, malignant pleural disease, and lung cancers). In the context of establishing...

Kitchenham, L., Nazal, B., Adcock, A. et al. 2022. Why does lifelong conventional housing reduce the sociability of female mice? Applied Animal Behaviour Science 246, 105532.

Compared to peers raised in well-resourced, 'enriched' environments (‘EE’), female laboratory mice from conventional barren cages are more aggressive to their cage-mates, and less sociable with familiar non-cage-mates (especially if these too are from conventional...

Denommé, M. R., Mason, G. J. 2022. Social buffering as a tool for improving rodent welfare. JAALAS 61(1), 5-14.

The presence of a conspecific can be calming to some species of animal during stress, a phenomenon known as social buffering. For rodents, social buffering can reduce the perception of and reaction to aversive experiences...

Davies, J. R., Purawijaya, D. A., Bartlett, J. M. et al. 2022. Impact of refinements to handling and restraint methods in mice. Animals 12(17), 2173.

There is increasing evidence that, compared to non-aversive handling methods (i.e., tunnel and cupping), tail handling has a negative impact on mouse welfare. Despite this evidence, there are still research organisations that continue to use...

Aldhshan, M. S., Mizuno, T. M. 2022. Effect of environmental enrichment on aggression and the expression of brain-derived neurotrophic factor transcript variants in group-housed male mice. Behavioural Brain Research 433, 113986.

Social and environmental factors influence behavior via modulation of brain physiological functions. Environmental enrichment (EE) is an animal housing technique that provides complex sensory, motor, and social stimulation, leading to modifications in the innate aggressiveness...

Fehrenbach, L. A., Adekanye, A. A., Palillo, M. B. et al. 2022. Internal temperatures of packaging for overnight cross-country shipping of zebrafish (Danio rerio). Comparative Medicine 72(3), 195-203.

As the use of zebrafish (Danio rerio) as a research model continues to rise, so too will the shipping and sharing of zebrafish strains across collaborating institutions. If done incorrectly, shipping can result in significant...

Barkus, C., Bergmann, C., Branco, T. et al. 2022. Refinements to rodent head fixation and fluid/food control for neuroscience. Journal of Neuroscience Methods 381, 109705.

The use of head fixation in mice is increasingly common in research, its use having initially been restricted to the field of sensory neuroscience. Head restraint has often been combined with fluid control, rather than...

Hohlbaum, K., Merle, R., Frahm, S. et al. 2022. Effects of separated pair housing of female C57BL/6JRj mice on well-being. Scientific Reports 12(1), 8819.

In laboratory animal facilities, it is a common code of practice to house female mice in groups. However, some experimental conditions require to house them individually, even though social isolation may impair their well-being. Therefore...

Nuber, M., Gonzalez-Uarquin, F., Neufurth, M. et al. 2022. Development of a 3D simulator for training the mouse in utero electroporation. PLOS ONE 17(12), e0279004.

In utero electroporation (IUE) requires high-level training in microinjection through the mouse uterine wall into the lateral ventricle of the mouse brain. Training for IUE is currently being performed in live mice as no artificial...

Brough, D. W., Murkin, J. T., Amos, H. E. et al. 2022. Comparing variability in measurement of subcutaneous tumors in mice using 3D thermal imaging and calipers. Comparative Medicine 72(6), 364–375.

Repeatable tumor measurements are key to accurately assessing tumor growth and treatment efficacy. A preliminary study that we conducted showed that a novel 3D and thermal imaging system (3D-TI) for measuring subcutaneous tumors in rodents...

Gilmour, K. M., Bard, B. 2022. Social buffering of the stress response: Insights from fishes. Biology Letters 18(10), 20220332.

Social buffering of stress refers to the effect of a social partner in reducing the cortisol or corticosterone response to a stressor. It has been well studied in mammals, particularly those that form pair bonds...

Ramos, J., Balasch, J. C., Tort, L. 2021. About welfare and stress in the early stages of fish. Frontiers in Veterinary Science 8, 634434.

In conclusion, the investigations carried out up to now demonstrate that during the early stages fish show high sensitivity to many types of stressors involving an array of responses to overcome alterations that could affect...

Bolt, L. M. 2021. Agonistic vocalization behaviour in the male ring-tailed lemur (Lemur catta). Primates 62(2), 417–430.

Vocalizations are used by group-living animals as aggressive and submissive signals during agonistic interactions, and are also used to maintain dominance hierarchies in many species. For gregarious strepsirrhines with large vocal repertoires and differentiated dominance...

Sørensen, D., Cloutier, S., Gaskill, B. (Eds.). 2021. Animal-centric Care and Management - Enhancing Refinement in Biomedical Research. CRC Press, Boca Raton, FL.

The concept of the 3Rs (Refinement, Reduction and Replacement) has been used as a framework for improving the welfare of laboratory animals for the last half century. By establishing an animal-centric view on housing and...

Perea, C., Vázquez-Ágredos, A., Ruiz-Leyva, L. et al. 2021. Caloric restriction in group-housed mice: Littermate and sex influence on behavioral and hormonal data. Frontiers in Veterinary Science 8, 639187.

Much of the research done on aging, oxidative stress, anxiety, and cognitive and social behavior in rodents has focused on caloric restriction (CR). This often involves several days of single housing, which can cause numerous...

Labitt, R. N., Oxford, E. M., Davis, A. K. et al. 2021. A validated smartphone-based electrocardiogram reveals severe bradyarrhythmias during immobilizing restraint in mice of both sexes and four strains. JAALAS 60(2), 201-212.

Mouse handling and restraint affect behavior, physiology, and animal welfare, yet little information is available on how various mouse restraint methods affect cardiovascular parameters. We validated the use of a smartphone-based ECG sys- tem in...

Ellis, T., Katsiadaki, I. 2021. Clarification of early end-points for refinement of animal experiments, with specific reference to fish. Laboratory Animals 55(3), 244-253.

Appropriate end-points are integral to the refinement of laboratory animal experiments. Our recent experience has highlighted that ambiguity around end-points is hampering their adoption in experiments that cause severe suffering to fish. In toxicology, the...

Koch, A. L., Rusnak, M., Peachee, K. et al. 2021. Comparison of the effects of osmotic pump implantation with subcutaneous injection for administration of drugs after total body irradiation in mice. Laboratory Animals 55(2), 142-149.

The increasing potential for radiation exposure from nuclear accidents or terrorist activities has intensified the need to develop pharmacologic countermeasures against injury from total body irradiation (TBI). Many initial experiments to develop and test these...

Huber, N., Mahr, K., Tóth, Z. et al. 2021. The stressed bird in the hand: Influence of sampling design on the physiological stress response in a free-living songbird. Physiology & Behavior 238, 113488.

Despite the widely used application of standardized capture-handling protocols to collect blood and assess the physiological stress response, the actual sampling design (e.g., timing and the number of blood samples) often differs between studies, and...

Seeley, K. E., Proudfoot, K. L., Wolfe, B. et al. 2021. Assessing allostatic load in ring-tailed lemurs (Lemur catta). Animals 11(11), 3074.

Responses to stress are unavoidable, adaptive mechanisms in humans and non-human animals. However, in humans, chronic stress has been linked to poor health outcomes and early mortality. Allostatic load, the physiologic dysregulation that occurs when...

Buckinx, A., Van Schuerbeek, A., Bossuyt, J. et al. 2021. Exploring refinement strategies for single housing of male C57BL/6JRj mice: Effect of cage divider on stress-related behavior and hypothalamic-pituitary-adrenal-axis activity. Frontiers in Behavioral Neuroscience 15, 743959.

Introduction: Single housing of laboratory mice is a common practice to meet experimental needs, or to avoid intermale aggression. However, single housing is considered to negatively affect animal welfare and may compromise the scientific validity...

da Silva Medeiros Elidio, H., Coelho, J. W. R., Cavalcanti Pereira da Silva, L. C. et al. 2021. Housing density and aggression in Syrian hamsters. JAALAS 60(5), 506-509.

The Syrian hamster (Mesocricetus auratus) is a solitary and naturally territorial animal, with female hamsters being more aggressive than males. This behavior makes handling difficult because they are usually housed in groups, which can lead...