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. 
Weaver, H. L., Carbaugh, C. M., Madejczyk, M. S. et al. 2024. Comparison of tricaine methanesulfonate (MS-222) and alfaxalone anesthesia in zebrafish (Danio rerio). JAALAS 63(1), 74–80.

The research use of zebrafish has risen exponentially over the past decade while anesthetic options have remained largely unchanged.6 ricaine methanesulfonate (MS-222) is widely accepted as an anesthetic for routine husbandry procedures, however it has...

Jorge, S., Félix, L., Costas, B. et al. 2023. Housing conditions affect adult zebrafish (Danio rerio) behavior but not their physiological status. Animals 13(6), 1120.

Zebrafish is a valuable model for neuroscience research, but the housing conditions to which it is exposed daily may be impairing its welfare status. The use of environmental enrichment and the refinement of methodology for...

Mauthe von Degerfeld, M., Serpieri, M., Bonaffini, G. et al. 2023. Intranasal atomization of ketamine, medetomidine and butorphanol in pet rabbits using a mucosal atomization device. Animals 13(13), 2076.

A non-invasive method of drug delivery, intranasal atomization, has shown positive results in human medicine and in some animal species. The objective of this study was to evaluate the effects of intranasal atomization, compared to...

Mirra, A., Maidanskaia, E. G., Carmo, L. P. et al. 2023. How is depth of anaesthesia assessed in experimental pigs? A scoping review. PLOS ONE 18(3), e0283511.

Despite the large number of pigs involved in translational studies, no gold standard depth of anaesthesia indicators are available. We undertook a scoping review to investigate and summarize the evidence that sustains or contradicts the...

Costea, R., Ene, I., Pavel, R. 2023. Pig sedation and anesthesia for medical research. Animals 13(24), 3807.

In clinical veterinary practice, proper training and expertise in anesthesia administration and monitoring are essential. Pigs are suitable experimental animals for many surgical techniques because they are similar in size to humans and have a...

Mirra, A., Hight, D., Kovacevic, A. et al. 2023. Sedline® miscalculation of depth of anaesthesia variables in two pigs due to electrocardiographic signal contamination. Animals 13(17), 2699.

Two young (11-week-old) pigs underwent sole propofol anaesthesia as part of an experimental study. The depth of anaesthesia was evaluated both clinically and using the electroencephalography(EEG)-based monitor Sedline; in particular, the patient state index, suppression...

Alizadeh, E. A., Graf, K., Schiwon, J. et al. 2023. Thirty years of telemetry-based data acquisition for cardiovascular drug safety evaluation: Applications and optimization. Journal of Pharmacological and Toxicological Methods 122, 107279.

Conducting safety evaluations of new drugs using conscious animals has been a specialty of our working group for thirty years. In this article, we review the various technical challenges and solutions dealt with over the...

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...

Midttun, H., Øverli, Ø., Tudorache, C. et al. 2022. Non-invasive sampling of water-borne hormones demonstrates individual consistency of the cortisol response to stress in laboratory zebrafish (Danio rerio). Scientific Reports 12(1) 6278.

Glucocorticoid (GC) stress hormones are well-known for their impact on phenotypic traits ranging from immune function to behaviour and cognition. For that reason, consistent aspects of an individual’s physiological stress response (i.e. GC responsiveness) can...

O'Malley, C. I., Hubley, R., Tambadou, H. et al. 2022. Refining restraint techniques for research pigs through habituation. Frontiers in Veterinary Science 9, 1016414.

Pigs are common research models and are strong animals that can be difficult to restrain. Improper restraint can put pigs and research personnel at risk for injury and induce stress, which can affect research outcomes...

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...

O’Malley, C. I., Hubley, R., Tambadou, H. et al. 2022. Refining restraint techniques for research pigs through habituation. Frontiers in Veterinary Science 9, 1016414.

Pigs are common research models and are strong animals that can be difficult to restrain. Improper restraint can put pigs and research personnel at risk for injury and induce stress, which can affect research outcomes...

Santymire, R. M., Young, M., Lenihan, E. et al. 2022. Preliminary investigation into developing the use of swabs for skin cortisol analysis for the ocean sunfish (Mola mola). Animals 12(20), 2868.

The ocean sunfish (mola; Mola mola) is the heaviest bony fish in the world. This slow-moving fish often is injured by fishing boats that use drift gillnets attributing to its listing as Vulnerable by the...

Söbbeler, F. J., Wendt, S., Briese, A. et al. 2022. Comparative study of pain-related responses of male piglets up to seven days of age to the application of different local anaesthetics and subsequent castration. Animals 12(20), 2833.

To evaluate pain responses to intratesticular and subscrotal injection of three local anaesthetics and their efficacy during castration a randomized controlled study was conducted. In groups of 20 piglets, procaine (2%), lidocaine (2%), or mepivacaine...

Wahltinez, S. J., Stacy, N. I., Hadfield, C. A. et al. 2022. Perspective: Opportunities for advancing aquatic invertebrate welfare. Frontiers in Veterinary Science 9, 973376.

Welfare considerations and regulations for invertebrates have lagged behind those for vertebrates, despite invertebrates comprising more than 95% of earth’s species. Humans interact with and use aquatic invertebrates for exhibition in zoos and aquaria, as...

Wang, M., Youssef, Al., Larsen, M. et al. 2021. Contactless video-based heart rate monitoring of a resting and an anesthetized pig. Animals 11(2), 442.

Heart rate (HR) is a vital bio-signal that is relatively easy to monitor with contact sensors and is related to a living organism’s state of health, stress and well-being. The objective of this study was...

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...

Prior, H., Holbrook, M. 2021. Strategies to encourage the adoption of social housing during cardiovascular telemetry recordings in non-rodents. Journal of Pharmacological and Toxicological Methods 108, 106959.

The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) is working with industry to promote social housing during cardiovascular telemetry recordings within non-rodent safety pharmacology and toxicology studies. Following surveys...

Chmurska-Gąsowska, M., Sowińska, N., Pałka, S. et al. 2021. Non-invasive measurement of thyroid hormones in domestic rabbits. Animals 11(5), 1194.

Thyroid hormones are essential for metabolism, energy homeostasis and reproduction. Hormones can be measured in various biological source materials: blood, feces, urine, saliva and others. The aim of our study was to verify usefulness of...

Ordóñez-Grande, B., Guerreiro, P. M., Sanahuja, I. et al. 2021. Environmental salinity modifies mucus exudation and energy use in European sea bass juveniles. Animals 11(6), 1580.

Changes in skin mucus production and composition offer a new means to study how fish cope with changes in the environment. We explored the utility of skin mucus as an indicator of physiological responses and...

Chang, L.-J., Ko, J. C., Weil, A. B. et al. 2021. Comparison of anesthetic and cardiorespiratory effects of tiletamine-zolazepam-detomidine-butorphanol, tiletamine-zolazepam-xylazine-butorphanol, and ketamine-detomidine-butorphanol in pigs. Journal of the AVMA 258(8), 883-891.

OBJECTIVE: To evaluate and compare the anesthetic, analgesic, and cardiorespiratory effects of tiletamine-zolazepam-detomidine-butorphanol (TZDB), tiletamine-zolazepam-xylazine-butorphanol (TZXB), and ketamine-detomidine-butorphanol (KDB) in pigs and to assess anesthetic recovery duration and quality following administration of tolazoline as a...

Ellis, T., Katsiadaki, I. 2021. Clarification of early end-points for refinement of animal experiments, with specific reference to fish. Laboratory Animals 55(3), 244-253.

Appropriate end-points are integral to the refinement of laboratory animal experiments. Our recent experience has highlighted that ambiguity around end-points is hampering their adoption in experiments that cause severe suffering to fish. In toxicology, the...

Kolarevic, J., Calduch-Giner, J., Espmark, Å. M. et al. 2021. A novel miniaturized biosensor for monitoring Atlantic salmon swimming activity and respiratory frequency. Animals 11(8), 2403.

The advanced development of sensor technologies has led to the emergence of fish biosensors that are currently used for research and commercial purposes. AEFishBIT is a miniaturized biosensor attached to fish operculum that measures physical...

Dalmau, A., Sánchez-Matamoros, A., Molina, J. M. et al. 2021. Intramuscular vs. intradermic needle-free vaccination in piglets: Relevance for animal welfare based on an aversion learning test and vocalizations. Frontiers in Veterinary Science 8, 715260.

The aim of the present study was to compare intramuscular injection with a needle and intradermic needle-free vaccinations against porcine reproductive and respiratory syndrome (PRRS) in piglets at 28 days old by studying behavioral and...

Abbo, L. A., Himebaugh, N. E., DeMelo, L. M. et al. 2021. Anesthetic efficacy of magnesium chloride and ethyl alcohol in temperate octopus and cuttlefish species. JAALAS 60(5), 556-567.

Cephalopods are important in biologic and biomedical research, yet relatively little objective information is available to guide researchers and veterinarians regarding the best methods for anesthetizing these animals for various experimental procedures. Recent studies demonstrate...