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. 
Attokaren, M. K., Jeong, N., Blanpain, L. et al. 2023. BrainWAVE: A flexible method for noninvasive stimulation of brain rhythms across species. ENeuro 10(2) ENEURO.0257-22.2022.

Rhythmic neural activity, which coordinates brain regions and neurons to achieve multiple brain functions, is impaired in many diseases. Despite the therapeutic potential of driving brain rhythms, methods to noninvasively target deep brain regions are...

Leyden, C., Brüggemann, T., Debinski, F. et al. 2022. Efficacy of tricaine (MS-222) and hypothermia as anesthetic agents for blocking sensorimotor responses in larval zebrafish. Frontiers in Veterinary Science 9, 864573.

Tricaine, or MS-222, is the most commonly used chemical anesthetic in zebrafish research. It is thought to act via blocking voltage-gated sodium channels, though its mechanism of action, particularly at the neuronal level, is not...

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...

Bissmire, H. 2022. Green clay: Not just for a pretty face. Animal Technology and Welfare 21(3), 242–243.

Mice can be prone to skin lesions for various reasons. Green clay is a non-invvasive method to treat such skin lesions, and does not require veterinary approval or have properties that may interfere with an...

Mason, G. J., Lavery, J. M. 2022. What is it like to be a bass? Red herrings, fish pain and the study of animal sentience. Frontiers in Veterinary Science 9, 788289.

Debates around fishes’ ability to feel pain concern sentience: do reactions to tissue damage indicate evaluative consciousness (conscious affect), or mere nociception? Thanks to Braithwaite’s research leadership, and concerns that current practices could compromise welfare...

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...

Owen, J. P., Kelsh, R. N. 2021. A suitable anaesthetic protocol for metamorphic zebrafish. PLOS ONE 16(3), e0246504.

Zebrafish are frequently used as a means to investigate development. These studies increasingly require repeated anaesthesia of zebrafish during juvenile (i.e. metamorphic) stages. The effects of anaesthesia during this time remain poorly studied. The aim...

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...

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...

Camargo-dos-Santos, B., Carlos, C. L., Favero-Neto, J. et al. 2021. Welfare in Nile tilapia production: Dorsal fin erection as a visual indicator for insensibility. Animals 11(10), 3007.

In aquaculture, to ensure animal welfare in pre-slaughter and slaughter stages, it is fundamental that fish are insensible. A method for evaluating fish insensibility is based on visual sensibility indicators (VSI) assessment (i.e., self-initiated behavior...

Jorge, S., Ferreira, J. M., Olsson, I. A. S. et al. 2021. Efficacy and behavioral recovery of different anesthetics. Zebrafish 18(5), 330-337.

The use of proper anesthesia in zebrafish research is essential to ensure fish welfare and data reliability. However, anesthesia long-term side effects remain poorly understood. The purpose of this study was to assess anesthesia quality...

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...

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...

Pedrazzani, A. S., Quintiliano, M. H., Bolfe, F. et al. 2020. Tilapia on-farm welfare assessment protocol for semi-intensive production systems. Frontiers in Veterinary Science 7, 606388.

The aim of this study was to develop and test a tilapia on-farm welfare assessment protocol, based on Brazilian semi-intensive production systems. The study included two mains steps: the elaboration of tilapia welfare protocol and...

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...

Musk, G. C., Ezzy, B. J., Kenchington, L. M. et al. 2020. A comparison of buffered tricaine methanesulfonate (MS-222) and isoeugenol anesthesia for caudal fin clipping in zebrafish (Danio rerio). JAALAS 59(6), 732-736.

The purpose of this study was to compare the safety and efficacy of buffered tricaine methanesulfonate (MS-222) and isoeugenol for the anesthesia of zebrafish undergoing caudal fin clipping. Eighty 9 mo Danio rerio (AB strain)...

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...

Stevens, C., Hawkins, P., Lovell-Badge, R. et al. 2019. Report of the 2018 RSPCA/UFAW Rodent and Rabbit Welfare Group meeting. Animal Technology and Welfare 18(2), 81-91.

The RSPCA/UFAW Rodent (and now Rabbit) Working Group has held a one-day meeting every autumn for the last 25 years, so that its members can discuss current welfare research, exchange views on welfare issues and...

Erickson, R. L., Blevins, C. E., De Souza Dyer, C. et al. 2019. Alfaxalone-xylazine anesthesia in laboratory mice (Mus musculus). JAALAS 58(1), 30-39.

Since its recent reformulation, alfaxalone has gained popularity as an injectable veterinary anesthetic, including promising studies demonstrating the use of alfaxalone-xylazine for anesthesia in mice. Here we sought to expand these studies by testing additional...

Sloman, K, A., Bouyoucos, I. A., Brooks, E. J. et al. 2019. Ethical considerations in fish research. Journal of Fish Biology 94(4), 556-577.

In this review, we focus primarily on the refinement of common methods used in fish research based on emerging knowledge with the aim of improving the welfare of fish used in scientific studies. We consider...

Martins, T., Valentim, A., Pereira, N. et al. 2019. Anaesthetics and analgesics used in adult fish for research: A review. Laboratory Animals 53(4), 325–341.

The number of fish used in research has increased in the last decades. Anaesthesia is required when fish must be held immobile and it is crucial to promote fish welfare, because these vertebrates can show...

Bauer, C., Schillinger, U., Brandl, J. et al. 2019. Comparison of pre-emptive butorphanol or metamizole with ketamine +medetomidine and s-ketamine + medetomidine anaesthesia in improving intraoperative analgesia in mice. Laboratory Animals 53(5), 459–469.

In accordance with the ‘refinement’ component of the 3Rs, the primary aim of this study was to investigate and compare ketamine + medetomidine (KM) and s-ketamine + medetomidine (SKM) anaesthetic protocols in C57BL/6J mice (both sexes). We sought to...

Gjendal, K., Lund Ottesen, J., Olsson, I. A. S. et al. 2019. Burrowing and nest building activity in mice after exposure to grid floor, isoflurane or ip injections. Physiology & Behavior 206, 59-66.

Burrowing and nest building are examples of highly motivated innate behaviours in rodents. Assessments based on these behaviours can be used as non-invasive indicators of pain, distress and suffering. In this study, we investigated the...

Jacobsen, J. V., Steen, K., Nilssen, K. J. 2019. Anaesthetic efficacy of Aqui-S, Benzoak, and MS-222 on lumpfish (Cyclopterus lumpus) fries. Impact from temperature, salinity, and fasting. PLOS ONE 14(1), e0211080.

Large numbers of lumpfish are produced for the Norwegian salmon industry and are used to combat sea lice infestations. Periodically high mortality of farmed lumpfish demonstrates the need to improve farming conditions and animal welfare...