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. 
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...

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...

Hirata, S. 2022. Sky after 30 years: A brief biography of three biomedical research chimpanzees in Japan. Primates 63(2), 105–108.

This article describes the strategies employed by Kumamoto Sanctuary in Japan to integrate 3 retired chimpanzees – who each spent 30 years singly housed in a biomedical facility – with the sanctuary’s other residents.

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...

Fehrenbach, L. A., Adekanye, A. A., Palillo, M. B. et al. 2022. Internal temperatures of packaging for overnight cross-country shipping of zebrafish (Danio rerio). Comparative Medicine 72(3), 195-203.

As the use of zebrafish (Danio rerio) as a research model continues to rise, so too will the shipping and sharing of zebrafish strains across collaborating institutions. If done incorrectly, shipping can result in significant...

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...

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...

Ramos, J., Balasch, J. C., Tort, L. 2021. About welfare and stress in the early stages of fish. Frontiers in Veterinary Science 8, 634434.

In conclusion, the investigations carried out up to now demonstrate that during the early stages fish show high sensitivity to many types of stressors involving an array of responses to overcome alterations that could affect...

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...

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...

Ross, S. R., Lake, B. R., Fultz, A. et al. 2021. An evaluation of thermal imaging as a welfare monitoring tool for captive chimpanzees. Primates 62(6), 919-927.

Among the growing list of novel tools with which to assess animal welfare is the use of thermal (infrared) imaging. The technology has already been utilized to identify emotional arousal in several nonhuman primate species...

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...

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...

Boers, K. L., Allender, M. C., Novak, L. J. et al. 2020. Assessment of hematologic and corticosterone response in free-living eastern box turtles (Terrapene carolina carolina) at capture and after handling. Zoo Biology 39(1), 13-22.

Hematology is a common tool for wildlife health assessments. Manual leukocyte counts are required in reptiles, however, disagreement between quantification methods has been observed in some chelonians. This study determined agreement between two methods of...

Plangsangmas, T., Brown, J., Thitaram, C. et al. 2020. Circadian rhythm of salivary immunoglobulin A and associations with cortisol as a stress biomarker in captive Asian elephants (Elephas maximus). Animals 10(1), 157.

Salivary immunoglobulin A (sIgA) has been proposed as a potential indicator of welfare for various species, including Asian elephants, and may be related to adrenal cortisol responses. This study aimed to distinguish circadian rhythm effects...

Hambrecht, S., Oerke, A.‐K., Heistermann, M. et al. 2020. Diurnal variation of salivary cortisol in captive African elephants (Loxodonta africana) under routine management conditions and in relation to a translocation event. Zoo Biology 39(3), 186–196.

The present study assessed the diurnal variation in salivary cortisol in captive African elephants during routine management (baseline) and in relation to a potential stressor (translocation) to evaluate to what extent acute stress may affect...

Cloutier Barbour, C., Danforth, M. D., Murphy, H. et al. 2020. Monitoring great ape heart health through innovative electrocardiogram technology: Training methodologies and welfare implications. Zoo Biology 39(6), 443-447.

Assessing and treating cardiovascular disease (or heart disease) is a growing concern for institutions housing great apes, as it is a major cause of mortality in all four taxa managed in human care. As part...

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)...

Schou, T. M., Palme, R., Malmkvist, J. et al. 2019. Relocation shortly after mating does not have a major impact on stress responses and reproduction in female farm mink. Applied Animal Behaviour Science 214, 89-94.

On farms, female mink are exposed to acute stressors multiple times due to handling, capturing and transport with restricted movement being a typical part of the mating procedure. We hypothesised that no relocation (group NON...

Kumar, V., Pradheeps, M., Kokkiligadda, A. et al. 2019. Non-invasive assessment of physiological stress in captive Asian elephants. Animals 9(8), 553.

Asian elephant (Elephas maximus) populations, both in the wild and in captivity, have been continually declining over the decades. The present study examined the physiological stress response of captive Asian elephants in relation to body...

Darbyshire, A. K., Oliver, K. H., Dupont, W. D. et al. 2019. Anesthesia and euthanasia of brine shrimp (Artemia franciscana). JAALAS 58(1), 58-63.

Invertebrates are often overlooked as laboratory animals, yet they are commonly used in toxicology, developmental, cellular and molecular biology, and radiation studies with euthanasia as an endpoint. Little is known regarding appropriate euthanasia methods for...

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...

Eichner, M., Garcia, K. 2019. Increase in morbidity and mortality in a shipment of red-eared slider turtles (Trachemys scripta elegans). Laboratory Animals 53(6), 634–640.

A cohort of captive-bred red-eared slider turtles, Trachemys scripta, was received from a commercial vendor. Shortly after arrival, several turtles presented as lethargic with subjectively pale skin and multifocal areas of cotton-like tufts in the...