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...

Imboden, T. J., Pownall, W. R., Rubin, S. et al. 2023. Determination of a safe sedative combination of dexmedetomidine, ketamine and butorphanol for minor procedures in dogs by use of a stepwise optimization method. Acta Veterinaria Scandinavica 65(1), 41.

In veterinary practice, most minor procedures such as radiographs, skin biopsies, and wound treatments require sedation. The combination of butorphanol, ketamine, and dexmedetomidine is commonly used, but the ideal dosages for this combination have not...

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...

Barton, J. C., Didier, M. D., Silvestrini, P. et al. 2022. A noninvasive method of temperature measurement using a noncontact handheld infrared thermometer fails to correlate with rectal temperature in dogs and cats. Journal of the American Veterinary Medical Association 260(7), 752-757.

OBJECTIVE: To perform a retrospective, multicenter observational study that compares the agreement of rectal temperature with the temperature measured with noncontact infrared thermometer (NCIT) in a population of dogs and cats. ANIMALS: 168 dogs and...

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...

van der Laan, J. E., Vinke, C. M., Arndt, S. S. 2022. Evaluation of hair cortisol as an indicator of long-term stress responses in dogs in an animal shelter and after subsequent adoption. Scientific Reports 12(1), 5117.

Shelter dogs are exposed to a variety of stressors. Among non-invasive techniques, hair cortisol concentration (HCC) is suggested an easy to collect biomarker for giving insight into long-term stress responses. We evaluated HCC as an...

van der Laan, J. E., Vinke, C. M., Arndt, S. S. 2022. Evaluation of hair cortisol as an indicator of long-term stress responses in dogs in an animal shelter and after subsequent adoption. Scientific Reports 12(1), 5117.

Shelter dogs are exposed to a variety of stressors. Among non-invasive techniques, hair cortisol concentration (HCC) is suggested an easy to collect biomarker for giving insight into long-term stress responses. We evaluated HCC as an...

Reicher, V., Bálint, A., Újváry, D. et al.2022. Non-invasive sleep EEG measurement in hand raised wolves. Scientific Reports 12(1), 9792.

Sleep research greatly benefits from comparative studies to understand the underlying physiological and environmental factors affecting the different features of sleep, also informing us about the possible evolutionary changes shaping them. Recently, the domestic dog...

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...

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...

Koshman, Y. E., Wilsey, A. S., Bird, B. M. et al. 2021. Automated blood sampling in canine telemetry studies: Enabling enhanced assessments of cardiovascular liabilities and safety margins. Journal of Pharmacological and Toxicological Methods 109, 107066.

Introduction: A successful integration of automated blood sampling (ABS) into the telemetry instrumented canine cardiovascular model is presented in this study. This combined model provides an efficient means to quickly gain understanding of potential effects...

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...

Wang, P., Ma, Y., Liang, F. et al. 2020. Non-contact vital signs monitoring of dog and cat using a UWB radar. Animals 10(2), 205.

As pets are considered members of the family, their health has received widespread attention. Since pets cannot talk and complain when they feel uncomfortable, monitoring vital signs becomes very helpful in disease detection, as well...

Byrnes, E. E., Lear, K. O., Morgan, D. L. et al. 2020. Respirometer in a box: Development and use of a portable field respirometer for estimating oxygen consumption of large‐bodied fishes. Journal of Fish Biology 96(4), 1045-1050.

Respirometry has become the standard method for measuring the metabolic rate of fishes. Traditionally, respirometry has required the fish to be kept in captivity and tested under controlled conditions; however, many species do not readily...

Tomasello, D. L., Sive, H. 2020. Noninvasive multielectrode array for brain and spinal cord local field potential recordings from live zebrafish larvae. Zebrafish 17(4), 271-277.

Zebrafish are an important and expanding experimental system for brain research. We describe a noninvasive electrophysiology technique that can be used in living larvae to measure spontaneous activity in the brain and spinal cord simultaneously...

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)...

McKenzie, D. J., Sadoul, B., Geffroy, B. 2019. Measuring cortisol, the major stress hormone in fishes. Journal of Fish Biology 94(4), 540-555.

Stress in teleosts is an increasingly studied topic because of its interaction with growth, reproduction, immune system and ultimately fitness of the animal. Whether it is for evaluating welfare in aquaculture, adaptive capacities in fish...

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...

Hampton, C. E., Riebold, T. W., Mandsager, R. E. 2019. Recovery characteristics of dogs following anesthesia induced with tiletamine-zolazepam, alfaxalone, ketamine-diazepam, or propofol and maintained with isoflurane. Journal of the American Veterinary Medical Association 254(12), 1421-1426.

OBJECTIVE To compare characteristics of recovery from isoflurane anesthesia in healthy nonpremedicated dogs after anesthetic induction by IV administration of tiletamine-zolazepam with those observed after induction by IV administration of alfaxalone, ketamine-diazepam, or propofol. DESIGN...

Lensen, C. M. M., Moons, C. P. H., Diederich, C. 2015. Saliva sampling in dogs: How to select the most appropriate procedure for your study. Journal of Veterinary Behavior 10(6), 504-512.

Saliva sampling is an easy, noninvasive method to assess short-term physiological changes, and as such is a valuable addition to behavioral studies in dogs. Different methods for collecting saliva samples in dogs have been reported...

Packer, R. M. A., Davies, A. M., Volk, H. A. 2019. What can we learn from the hair of the dog? Complex effects of endogenous and exogenous stressors on canine hair cortisol. PLOS ONE 14(5), e0216000.

Hair is an emerging biological matrix in which to measure chronic HPA axis activity, offering a longer term view into an animal’s life. We explored effects of exogenous (e.g. lifestyle, medications, social environment) and endogenous...

Ehrlich, O., Karamalakis, A., Krylov, A. J. et al. 2019. Clove oil and AQUI-S efficacy for zebrafish embryo, larva, and adult anesthesia. Zebrafish 16(5), 451-459.

Since the use of the zebrafish Danio rerio genetic model organism within the scientific research community continues to grow rapidly, continued procedural refinement to support high-quality, reproducible research and improve animal welfare remains an important...