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. 
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...

Mieske, P., Hobbiesiefken, U., Fischer-Tenhagen, C. et al. 2022. Bored at home?—A systematic review on the effect of environmental enrichment on the welfare of laboratory rats and mice. Frontiers in Veterinary Science 9, 899219.

Boredom is an emotional state that occurs when an individual has nothing to do, is not interested in the surrounding, and feels dreary and in a monotony. While this condition is usually defined for humans...

Hepps Keeney, C., Harrison, T. M. 2022. Euthanasia complications in non-domestic species. Journal of Zoological and Botanical Gardens 3(4), 616–623.

There are very few studies describing euthanasia complications in non-domestic species. The goal of this study was to survey veterinarians to determine what complications may commonly occur during the euthanasia of non-domestic species. An online...

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...

Schalbetter, S. M., Mueller, F. S., Scarborough, J. et al. 2021. Oral application of clozapine-N-oxide using the micropipette-guided drug administration (MDA) method in mouse DREADD systems. Lab Animal 50, 69-75.

The designer receptor exclusively activated by designer drugs (DREADD) system is one of the most widely used chemogenetic techniques to modulate the activity of cell populations in the brains of behaving animals. DREADDs are activated...

Teixeira-Santos, L., Albino-Teixeira, A., Pinho, D. 2021. An alternative method for oral drug administration by voluntary intake in male and female mice. Laboratory Animals 55(1), 76-80.

Drug administration to experimental rodents is often invasive and stressful, thus reducing animal welfare and potentially confounding experimental results. Methods of oral drug delivery in which rodents cooperate voluntarily minimize stress, pain and morbidity. We herein...

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...

Stevens, C., Hawkins, P., Smulders, T. V. et al. 2021. Report of the 2020 RSPCA/UFAW rodent and rabbit welfare meeting. Animal Technology and Welfare 20(1), 21-33.

The RSPCA/UFAW rodent and rabbit welfare group has held a one-day meeting every autumn for the last 27 years, so that its members can discuss current welfare research, exchange views on welfare issues and share...

Kay, W. R., Mawson, P. R. 2021. An efficient method for the euthanasia of cane toads (Rhinella marina) under northern Australian field conditions. Animals 11(8), 2239.

The euthanasia of cane toads under field conditions presents a number of logistical and animal welfare challenges. One recommended method of control involves the use of carbon dioxide in plastic bags. This paper describes the...

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...

Campbell, D. L. M., Lee, C. 2021. A perspective on strategic enrichment for brain development: Is this the key to animal happiness? Frontiers in Veterinary Science 8, 720422.

Livestock animals are sentient beings with cognitive and emotional capacities and their brain development, similar to humans and other animal species, is affected by their surrounding environmental conditions. Current intensive production systems, through the restrictions...

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...

Verjat, A., Devienne, P., Rödel, H. G. et al. 2021. More exploratory house mice judge an ambiguous situation more negatively. Animal Cognition 24(1), 53–64.

Exploration tendency, one of the most investigated animal personality traits, may be driven by either positive (when seeking interesting information) or negative (to reduce the uncertainty of the environment) affective/emotional profiles. To disentangle the valence...

Baciadonna, L., Briefer, E. F., McElligott, A. G. 2020. Investigation of reward quality-related behaviour as a tool to assess emotions. Applied Animal Behaviour Science 225, 104968.

Animals are likely to appraise events as positive or negative based on their subjective perception, current state and past experiences. We tested the effects of anticipating positive (food anticipation), negative (inaccessible food) and neutral (clicker...

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...

Reinhardt, V. (ed.) 2020. It’s Okay to Cry - Discussions by the Laboratory Animal Refinement & Enrichment Forum [LAREF], Volume V. Animal Welfare Institute, Washington, DC.

This is the 5th volume of selected discussions that took place on the electronic Laboratory Animal Refinement & Enrichment Forum between February 2016 and December 2019. The forum was created in October 2002; it allows...

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...

Galex, I. A., Gallant, C. M., D'Avignon, N. et al. 2020. Evaluation of effective and practical euthanasia methods for larval African clawed frogs (Xenopus laevis). JAALAS 59(3), 269–274.

Larval, or tadpole-stage Xenopus laevis frogs are a popular research model for developmental biology and disease studies. Existing euthanasia guidance documents offer recommendations for both eggs and adult stages, yet do not specifically address the...

Natusch, D. J. D., Aust, P. W., Khadiejah, S. et al. 2020. Behavioral and corticosterone responses to carbon dioxide exposure in reptiles. PLOS ONE 15(10), e0240176.

The use of carbon dioxide (CO2) exposure as a means of animal euthanasia has received considerable attention in mammals and birds but remains virtually untested in reptiles. We measured the behavioral responses of four squamate...