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. 
Justin, M., Jež, M., Košir, A. et al. 2021. Application of the 3R principles: Vertebrae as an additional source of murine bone-marrow cells. Laboratory Animals 55(1), 43-52.

Experimental murine models are an essential tool in the field of bone marrow (BM) transplantation research. Therefore, numerous mice are required to obtain a sufficient number of BM cells, which is in contrast with the...

Améndola, L., Ratuski, A., Weary, D. M. 2021. Individual differences in rat sensitivity to CO2. PLOS ONE 16(1), e0245347.

Feelings of fear, anxiety, dyspnea and panic when inhaling carbon dioxide (CO2) are variable among humans, in part due to differences in CO2 sensitivity. Rat aversion to CO2 consistently varies between individuals; this variation in...

Blaney, A., Jampachaisri, K., Huss, M. K. et al. 2021. Sustained release buprenorphine effectively attenuates postoperative hypersensitivity in an incisional pain model in neonatal rats (Rattus norvegicus). PLOS ONE 16(2), e0246213.

Despite the need for safe and effective postoperative analgesia in neonates, research regarding pain management in neonatal rodents is relatively limited. Here, we investigate whether sustained release buprenorphine (Bup SR) effectively attenuates thermal hypersensitivity in...

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...

Giménez-Llort, L., Torres-Lista, V. 2021. Social nesting, animal welfare, and disease monitoring. Animals 11(4), 1079.

The assessment of welfare and disease progression in animal models is critical. Most tools rely on evaluating individual subjects, whereas social behaviors, also sensitive to acute illness, chronic diseases, or mental health, are scarcely monitored...

Silva-Reis, R., Faustino-Rocha, A. I., Gonçalves, M. et al. 2021. Refinement of animal model of colorectal carcinogenesis through the definition of novel humane endpoints. Animals 11(4), 985.

This study aimed to define appropriate humane endpoints (HEs) for an animal model of colorectal carcinogenesis (CRC). Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2) injected with ethylenediamine tetraacetic acid...

Vis, A., Lammers, J. C. A. M., de Vroege, R. et al. 2021. Strategies to improve survival from surgery for heart valve implantation in sheep. Comparative Medicine 71(3), 235-239.

Sheep are a commonly used and validated model for cardiovascular research and, more specifically, for heart valve research. Implanting a heart valve on the arrested heart in sheep is complex and is often complicated by...

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...

Xu, J. J., Thurston, S. E., Robinson, T. J. et al. 2021. Effects of analgesics on tumor growth in mouse models of prostate cancer bone metastasis. JAALAS 60(3), 341-348.

Murine models of tumor development often require invasive procedures for tumor implantation, potentially causing pain or distress. However, analgesics are often withheld during implantation because of concerns that they may adversely affect tumor development. Previous...

Krueger, L. D., Chang, S. E., Motoc, M. et al. 2021. Effects of pair housing on patency of jugular catheters in rats (Rattus norvegicus). JAALAS 60(3), 357-364.

Chronic vascular access devices are widely used in a variety of species for repeated blood sampling or substance administration. Jugular catheters are commonly used for studying addiction-related behaviors in rats. Rats with catheters have historically...

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...

Komatsu, T., Ohta, H., Motegi, H. et al. 2021. A novel model of ischemia in rats with middle cerebral artery occlusion using a microcatheter and zirconia ball under fluoroscopy. Scientific Reports 11(1), 12806.

Here, we present a highly selective rat MCAO model by percutaneous caudal arterial puncture using a microcatheter and zirconia ball under fluoroscopic guidance. The model is predictable and reproducible, which is well confined within the...

Yu, J. H., Brown, J., Boisseau, N. et al. 2021. Effects of Lupron and surgical castration on fecal androgen metabolite concentrations and intermale aggression in capybaras (Hydrochoerus hydrochaeris). Zoo Biology 40(2), 135-141.

To curb agonistic interactions in a bachelor group of three male capybaras (Hydrochoerus hydrochaeris), a single dose of leuprolide acetate (Lupron®) was used in an attempt to chemically sterilize the males. Concurrently, fecal androgen metabolite...

Kimm, S., Rauterberg, S. L., Bill, J. et al. 2021. Use of space, active and resting behaviour in fattening rabbits (Oryctolagus cuniculus) housed in a combi park system: A case study. Animal Welfare 30(4), 493-506.

In this case study, a housing system for rabbits (Oryctolagus cuniculus) was developed, complying with the new German Welfare Regulation, and evaluated on-farm with regard to the rabbits' behaviour during four fattening periods. The housing...

Xie, W., Kordt, M., Palme, R. et al. 2021. Diagnostic ability of methods depicting distress of tumor-bearing mice. Animals 11(8), 2155.

Subcutaneous tumor models in mice are the most commonly used experimental animal models in cancer research. To improve animal welfare and the quality of scientific studies, the distress of experimental animals needs to be minimized...

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...

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...

Xie, W., Palme, R., Schafmayer, C. et al. 2021. Distress analysis of mice with cervical arteriovenous fistulas. Animals 11(11), 3051.

The welfare of laboratory animals is a consistent concern for researchers. Its evaluation not only fosters ethical responsibility and addresses legal requirements, but also provides a solid basis for a high quality of research. Recently...

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...

Bennett, T. E., Pavek, T. J., Schwark, W. S. et al. 2021. Comparison of nociceptive effects of buprenorphine, firocoxib, and meloxicam in a plantar incision model in Sprague–Dawley rats. JAALAS 60(5), 539-548.

Due to their reduced frequency of dosing and ease of availability, NSAIDs are generally preferred over opioids for rodent analgesia. We evaluated the efficacy of the highly COX2-selective NSAID firocoxib as compared with meloxicam and...

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...

Winn, C. B., Hwang, S. K., Morin, J. et al. 2021. Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models. PLOS ONE 16(9), e0257694.

In oncology research, while xenograft tumor models are easily visualized and humane endpoints can be clearly defined, metastatic tumor models are often based on more subjective clinical observations as endpoints. This study aimed at identifying...

Miller, A. L., Roughan, J. V. 2021. Welfare assessment, end-point refinement and the effects of non-aversive handling in C57BL/6 mice with Lewis lung cancer. Animals 12(1), 23.

Cancer-bearing mice are at risk of developing anxiety, pain, or malaise. These conditions may not only harm welfare but could also undermine data quality and translational validity in studies to develop therapeutic interventions. We aimed...

Weegh, N., Zentrich, E., Zechner, D. et al. 2021. Voluntary wheel running behaviour as a tool to assess the severity in a mouse pancreatic cancer model. PLOS ONE 16(12), e0261662.

Laboratory animals frequently undergo routine experimental procedures such as handling, restraining and injections. However, as a known source of stress, these procedures potentially impact study outcome and data quality. In the present study, we, therefore...