Refinement Database

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

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

Links to the full text for publications that appear in open access journals or are published on the AWI website are provided under the abstract.

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 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. Most publications older than 2010 can only be searched by keyword. 
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...
Hickman, D. L. 2022. Minimal exposure times for irreversible euthanasia with carbon dioxide in mice and rats. JAALAS 61(3), 283-286.
When using an anesthetic overdose to euthanize laboratory rodents, a secondary method of euthanasia is recommended to ensure that the apparent death is irreversible. This secondary method usually is accomplished through the collection of tissues...
McKinney, M. M., Dupont, W. D., Corson, K. J. et al. 2022. Physiologic and behavioral effects in mice anesthetized with isoflurane in a red-tinted or a traditional translucent chamber. JAALAS 61(4), 322-332.
Isoflurane has been characterized as a distressing agent for rodents, causing both physiologic and behavioral effects. Using a "darkened home cage" has been recommended during CO2 administration for rodent euthanasia; this is arguably a similar...
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...
Clarkson, J. M., Martin, J. E., McKeegan, D. E. F. 2022. A review of methods used to kill laboratory rodents: Issues and opportunities. Laboratory Animals 56(5), 419-436.
Rodents are the most widely used species for scientific purposes. A critical pre-requisite of their use, based on utilitarian ethical reasoning, is the provision of a humane death when necessary for scientific or welfare grounds...
MacLellan, A., Nazal, B., Young et al. 2022. Waking inactivity as a welfare indicator in laboratory mice: Investigating postures, facial expressions and depression-like states. Royal Society Open Science 9(11), 221083.
Animal welfare assessment relies on valid and practical indicators of affect. In mice, the most widely used research vertebrates, lying still with eyes open, inactive-but-awake (IBA) in the home cage, has potential to be one...
Novak, J., Jaric, I., Rosso, M. et al. 2022. Handling method affects measures of anxiety, but not chronic stress in mice. Scientific Reports 12(1), 20938.
Studies in mice have shown that less aversive handling methods (e.g. tunnel or cup handling) can reduce behavioural measures of anxiety in comparison to picking mice up by their tail. Despite such evidence, tail handling...
Hickman, D. L. 2021. Wellbeing of mice euthanized with carbon dioxide in their home cage as compared with an induction chamber. JAALAS 60(1), 72-76.
The AVMA Guidelines on Euthanasia state that, to decrease potential distress of animals, the home cage should be used for the euthanasia of mice. The current study evaluated this recommendation by comparing behavioral and physiologic...
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...
Navarro, K. L., Huss, M., Smith, J. C. et al. 2021. Mouse anesthesia: The art and science. ILAR Journal 62(1-2), 238-273.
There is an art and science to performing mouse anesthesia, which is a significant component to animal research. Frequently, anesthesia is one vital step of many over the course of a research project spanning weeks...
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...
Blevins, C. E., Celeste, N. A., Marx, J. O. 2021. Effects of oxygen supplementation on injectable and inhalant anesthesia in C57BL/6 mice. JAALAS 60(3), 289-297.
Oxygen supplementation is rarely considered when anesthetizing laboratory mice, despite reports that mice become profoundly hypoxic under anesthesia. Little is known about the effects of hypoxia on anesthetic performance. This article focuses on the effects...
Travain, T., Valsecchi, P. 2021. Infrared thermography in the study of animals’ emotional responses: A critical review. Animals 11(9), 2510.
Whether animals have emotions was historically a long-lasting question but, today, nobody disputes that they do. However, how to assess them and how to guarantee animals their welfare have become important research topics in the...
Rodriguez-Sanchez, R., Barnaby, E., Améndola, L. et al. 2021. Voluntary oral ingestion of a sedative prior to euthanasia with CO2: Behavioural responses of mice. Animals 11(10), 2879.
Laboratory mice are commonly euthanised with carbon dioxide (CO2); however, there is ample evidence that this gas is aversive. Previous work suggests that sedation achieved via injection with benzodiazepines prior to CO2 administration could reduce...
MacLellan, A., Fureix, C., Polanco, A. et al. 2021. Can animals develop depression? An overview and assessment of “depression-like” states. Behaviour 158(14/15), 1303–1353.
Describing certain animal behaviours as 'depression-like' or 'depressive' has become common across several fields of research. These typically involve unusually low activity or unresponsiveness and/or reduced interest in pleasure (anhedonia). While the term 'depression-like' carefully...
Brunt, M. W., Améndola, L., Weary, D. M. 2021. Attitudes of laboratory animal professionals and researchers towards carbon dioxide euthanasia for rodents and perceived barriers to change. Laboratory Animals 55(6), 531-539.
Evidence indicates that carbon dioxide (CO2) induces negative affective states (including anxiety, fear and distress) in laboratory rodents, but many countries still accept it for euthanasia. Alternative methods (e.g. inhalant anaesthetic) may represent a refinement...
Redaelli, V., Bosi, A., Luzi, F. et al. 2021. Neuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study. PLoS ONE 16(11), e0259938.
Background: Animal models used to study pathologies requiring rehabilitation therapy, such as cardiovascular and neurologic disorders or oncologic disease, must be as refined and translationally relevant as possible. Sometimes, however, experimental procedures such as those...
Gjendal, K., Ottesen, J. L., Olsson, I. et al. 2020. Effect of repeated exposure to isoflurane on nest building and burrowing in mice. JAALAS 59(1), 30–36.
Nest building and burrowing are highly motivated natural behaviors in rodents, and changes in these behaviors can serve as welfare assessment tools. In this study, we investigated: 1) the limits of agreement between 2 observers...
Turner, P. V., Hickman, D. L., van Luijk, J. et al. 2020. Welfare impact of carbon dioxide euthanasia on laboratory mice and rats: A systematic review. Frontiers in Veterinary Science 7, 411.
Background: There has been increased concern about the suitability of CO2 as a method for euthanasia of laboratory mice and rats, including the potential discomfort, pain or distress that animals may experience prior to loss...
Tang, W., Zillmann, U., Sprengel, R. 2020. Alternative anesthesia of neonatal mice for global rAAV delivery in the brain with non-detectable behavioral interference in adults. Frontiers in Behavioral Neuroscience 14, 115.
Viral-transduced gene expression is the current standard for cell-type-specific labeling and cell tacking in experimental neuroscience. To achieve widespread gene expression, a viral delivery method to neonatal rodents was introduced more than two decades ago...
Shomer, N. H., Allen-Worthington, K. H., Hickman, D. L. et al. 2020. Review of rodent euthanasia methods. JAALAS 59(3), 242–253.
The optimal choice of euthanasia method for laboratory rodents depends on a number of factors, including the scientific goals of the study, the need to minimize animal pain and/or distress, applicable guidelines and laws, the...
Laferriere, C. A., Pang, D. S. 2020. Review of intraperitoneal injection of sodium pentobarbital as a method of euthanasia in laboratory rodents. JAALAS 59(3), 254–263.
Euthanasia is one of the most commonly performed procedures in biomedical research, involving tens of millions of animals in North America and Europe every year. The use of sodium pentobarbital, injected intraperitoneally, for killing rodents...
Laferriere, C. A., Leung, V. S., Pang, D. S. 2020. Evaluating intrahepatic and intraperitoneal sodium pentobarbital or ethanol for mouse euthanasia. JAALAS 59(3), 264–268.
Intraperitoneal (IP) injection of sodium pentobarbital (PB) is an accepted method of euthanasia for mice. However, this method has important drawbacks, including the potential for pain or misinjection. The objective of this prospective, randomized, blinded...
Gergye, C. H., Zhao, Y., Moore, R. et al. 2020. A comparison of ketamine or etomidate combined with xylazine for intraperitoneal anesthesia in four mouse strains. JAALAS 59(5), 519-530.
Intraperitoneal (IP) injection is a common route of anesthetic administration in mice. Ketamine-xylazine (KX) anesthesia is one of the most widely used IP protocols, but has limitations. Etomidate is an alternative to ketamine that has...
Ho, H., Fowle, A., Coetzee, M. et al. 2020. An inhalation anaesthesia approach for neonatal mice allowing streamlined stereotactic injection in the brain. Journal of Neuroscience Methods 342, 108824.
Background: Investigating brain function requires tools and techniques to visualise, modify and manipulate neuronal tissue. One powerful and popular method is intracerebral injection of customised viruses, allowing expression of exogenous transgenes. This technique is a...

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