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. 
Zevnik, B., Jerchow, B., Buch, T. 2022. 3R measures in facilities for the production of genetically modified rodents. Lab Animal 51(6), 162-177.

Sociocultural changes in the human–animal relationship have led to increasing demands for animal welfare in biomedical research. The 3R concept is the basis for bringing this demand into practice: Replace animal experiments with alternatives where...

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...

Hwang, S.-K., Tyszkiewicz, C., Dragon, M. et al. 2022. Introduction of gloved hand to cage induces 22-kHz ultrasonic vocalizations in male albino rats. PLOS ONE 17(11), e0278034.

Rodents emit ultrasonic vocalizations (USVs) above the human hearing threshold of ~ 20 kHz to communicate emotional states and to coordinate their social interactive behavior. Twenty-two kHz USVs emitted by adult rats have been reported...

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...

Assenmacher, C.-A., Lanza, M., Tarrant, J. C. et al. 2022. Post mortem study on the effects of routine handling and manipulation of laboratory mice. Animals 12(23), 3234.

Routine handling and manipulation of laboratory mice are integral components of most preclinical studies. Any type of handling and manipulation may cause stress and result in physical harm to mice, potentially leading to unintended consequences...

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...

Reifenrath, J., Heider, M., Kempfert, M. et al. 2022. Buprenorphine in rats: Potent analgesic or trigger for fatal side effects? Acta Veterinaria Scandinavica 64(1), 37.

With ongoing animal welfare efforts, multimodal analgesia is often recommended to implement in study protocols. Buprenorphine with very potent analgesic effect is a standard opioid for the use in this context in rats. In this...

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...

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...

Suba-Bokodi, É., Nagy, I., Molnár, M. 2022. Changes in the stress tolerance of dwarf rabbits in animal-assisted interventions. Applied Sciences 12(14), 6979.

Background: Rabbits are common companion animals in many European countries. Rabbit-assisted interventions in primary schools are suitable for decreasing the anxiety levels of children, which may increase the education efficiency of teachers. Methods: In our...

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...

Kendall, L. V., Singh, B., Bailey, A. L. et al. 2021. Pharmacokinetics and efficacy of a long-lasting, highly concentrated buprenorphine solution in mice. JAALAS 60(1), 64-71.

Buprenorphine is a commonly used opioid for mitigating pain in laboratory mice after surgical procedures; however, the dosing interval necessary for standard buprenorphine may require treatment every 4 to 6 h to maintain an adequate...

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...

Katz, E. M., Huss, M. K., Jampachaisri, K. et al. 2021. Buprenorphine, but not lidocaine, effectively attenuates post-operative thermal hypersensitivity in an incisional model in neonatal rats (Rattus norvegicus). Scandinavian Journal of Laboratory Animal Science 47(1), 1-11.

There is limited information on safe and effective neonatal rodent analgesia. The aim of this study was to evaluate the efficacy and duration of analgesia provided by buprenorphine (Bup) and lidocaine (Lid) in an incisional...

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...

Bombail, V., Brown, S. M., Hammond, T. J. et al. 2021. Crying with laughter: Adapting the tickling protocol to address individual differences among rats in their response to playful handling. Frontiers in Veterinary Science 8, 677872.

In this Opinion paper, we consider whether current methods of tickling overemphasize the use of pinning (Figure 1) to which there may be a wider response variation than commonly acknowledged. We do not dispute that...

Song, M. K., Lee, J. H., Kim, Y.-J. 2021. Effect of chronic handling and social isolation on emotion and cognition in adolescent rats. Physiology & Behavior 237, 113440.

Adolescence is a critical period of establishing social relations through social interactions that affect the emotional development associated with stress responses, anxiety, depression, and cognitive development. We investigated the behavioral and neurobiological changes induced by...

Moore, J., Wickert, M. 2021. Thinking outside of the tunnel for non-aversive mouse handling. Animal Technology and Welfare 20(2), 161-163.

The key to non-aversive methods of handling lies in understanding what capture method creates the least anxiety in mice: be this tunnel or cupping or another method. It is important that we do not get...

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...

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...

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...

Sandgren, R., Grims, C., Waters, J. et al. 2021. Using cage ladders as a handling device reduces aversion and anxiety in laboratory mice, similar to tunnel handling. Scandinavian Journal of Laboratory Animal Science 47(5), 31-41.

Handling laboratory animals for husbandry and other procedures can be an important source of anxiety and stress, compromising animal welfare as well as the reliability of research that is sensitive to background stressors. Studies have...