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...

Chakravarty, S., Donoghue, J., Waite, A. S. et al. 2023. Closed-loop control of anesthetic state in nonhuman primates. PNAS Nexus 2(10), 293.

Research in human volunteers and surgical patients has shown that unconsciousness under general anesthesia can be reliably tracked using real-time electroencephalogram processing. Hence, a closed-loop anesthesia delivery (CLAD) system that maintains precisely specified levels of...

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...

Buckmaster, C. L., Levesque, D., LaFollette, M. et al. 2022. Five hot topics in refinement of nonhuman primate neuroscience research. Laboratory Animal Science Professional 10(1) (January/February), 24-26.

Members of the North American 3Rs Collaborative (NA3RsC) refinement initiative have chosen to summarize developments in five hot topics of interest: 1. Tips for welfare-friendly transport, chairing, and restraint; 2. Guidance on refining food and...

Guerrero-Martin, S. M., Brill, S., Carlson, B. W. 2022. Development and implementation of a positive reinforcement training program for nonhuman primates in biomedical research. Laboratory Animal Science Professional 10(1) (January/February), 48-52.

Despite clear benefits of PRT for NHPs and biomedical research, investigators often view the investment in personnel expertise and time required to train animals as deterrents towards adopting PRT. We provide an example of how...

Bethell, E. J., Khan, W., Hussain, A. 2022. A deep transfer learning model for head pose estimation in rhesus macaques during cognitive tasks: Towards a nonrestraint noninvasive 3Rs approach. Applied Animal Behaviour Science 255, 105708.

Head orientation is a measure of attention used in behavioral psychological research with non-human primates. It is used across a broad range of disciplines and settings, from the field to the laboratory. Field methods are...

Jacob, G., Katti, H., Cherian, T. et al. 2021. A naturalistic environment to study visual cognition in unrestrained monkeys. eLife 10, e63816.

Macaque monkeys are widely used to study vision. In the traditional approach, monkeys are brought into a lab to perform visual tasks while they are restrained to obtain stable eye tracking and neural recordings. Here...

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...

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...

Leeds, A., Boyer, D., Ross, S. R. et al. 2021. Patterns of wounding in mixed-sex social groups of western lowland gorillas (Gorilla gorilla gorilla). Applied Animal Behaviour Science 236, 105226.

Long-term, multi-institutional assessments have become a reliable tool for evaluating patterns of wounding in zoo-living primates, with results informing on best practices for species-specific care protocols and population management strategies. For western lowland gorillas (Gorilla...

Haertel, A. J., Schultz, M. A., Colgin, L. M. et al. 2021. Predictors of subcutaneous injection site reactions to sustained-release buprenorphine in rhesus macaques (Macaca mulatta). JAALAS 60(3), 329-336.

Subcutaneous injection site reactions to sustained-release buprenorphine hydrochloride (Buprenorphine SR) in macaques have been reported in only a single case report. In the current study, we evaluated the incidence rate and predictors of buprenorphine SR...

Houser, L. A., Ramsey, C., de Carvalho, F. M. et al. 2021. Improved training and semen collection outcomes using the closed box chair for macaques. Animals 11(8), 2384.

Collaborative semen collection in monkeys is a valuable tool in research, animal collection management, and conservation efforts. To obtain samples, monkeys are often restrained in open restraint chairs (ORC) with the “pole and collar” technique...

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...

Falendysz, E. A., Calhoun, D. M., Smith, C. A. et al. 2020. Outside the box: Working with wildlife in biocontainment. ILAR Journal 61(1), 72-85.

Research with captive wildlife in Animal Biosafety Level 2 (ABSL2) and 3 (ABSL3) facilities is becoming increasingly necessary as emerging and re-emerging diseases involving wildlife have increasing impacts on human, animal, and environmental health. Utilizing...

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...

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...

Zemanova, M. A. 2020. Towards more compassionate wildlife research through the 3Rs principles: Moving from invasive to noninvasive methods. Wildlife Biology 2020(1), no page numbers.

Research in ecology and wildlife biology remains crucial for increasing our knowledge and improving species management and conservation in the midst of the current biodiversity crisis. However, obtaining information on population status often involves invasive...

Reinhardt, V. (ed.) 2020. It’s Okay to Cry - Discussions by the Laboratory Animal Refinement & Enrichment Forum [LAREF], Volume V. Animal Welfare Institute, Washington, DC.

This is the 5th volume of selected discussions that took place on the electronic Laboratory Animal Refinement & Enrichment Forum between February 2016 and December 2019. The forum was created in October 2002; it allows...

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...

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)...

Engel, R. M., Thomas III, M. L., Banks, R. E. 2019. Regional anesthesia for dentistry and orofacial surgery in rhesus macaques (Macaca mulatta). JAALAS 58(2), 223-230.

Regional anesthesia is a commonly used adjunct to orofacial dental and surgical procedures in companion animals and humans. However, appropriate techniques for anesthetizing branches of the mandibular and maxillary nerves have not been described for...

Association of Primate Veterinarians. 2019. Association of Primate Veterinarians’ guidelines for nonhuman primate restraint. JAALAS 58(3), 282-284.

The Association of Primate Veterinarians (APV) recognizes that several forms of restraint, including physical and chemical, are necessary for the safe handling of nonhuman primates (NHPs). The following guidelines aim to provide information to researchers...

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...