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...

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...

Koperski, P. 2023. It is not only data—Freshwater invertebrates misused in biological monitoring. Animals 13(16), 2570.

The article presents and discusses the issues of the use of free-living invertebrates to assess the ecological status of freshwater environments with different methods of biological monitoring. Invertebrates are excluded from ethical consideration in the...

Brown, A. 2023. Aced it! Performing large volume survival bleeds in rabbits. Laboratory Animal Science Professional 11(3) (May/June), 44-46.

New Zealand White rabbits are commonly used for polyclonal antibody production, which can require collecting no more than 10% of total body weight every two weeks (approximately 20 ml of blood for a 4 kg...

Bertani, S., Donadi, A., Franchi, J. et al. 2023. Blood microsampling in cynomolgus monkey and evaluation of plasma PK parameters in comparison to conventional sampling. Journal of Pharmacological and Toxicological Methods 123, 107298.

Microsampling, a reduced volume sampling method, has successfully gained attention at the International Conference on Harmonization (ICH) level and established benefits support its use in Toxicokinetic (TK) studies. These improved sampling techniques are less invasive...

Costa, R. S., Ciotti-McClallen, M., Tilley, R. et al. 2023. Intramuscular alfaxalone with or without buprenorphine or hydromorphone provides sedation with minimal adverse effects in healthy rabbits (Oryctolagus cuniculus) in a randomized blinded controlled trial. Journal of the American Veterinary Medical Association 261(2), 223–228.

OBJECTIVE To evaluate the effects of alfaxalone administered IM with or without buprenorphine or hydromorphone in healthy rabbits (Oryctolagus cuniculus). ANIMALS 24 male rabbits undergoing elective orchiectomy between August 21, 2021, and November 6, 2021...

Gilberto, D., Michener, M., Smith, B. et al. 2022. Chronic collection of cerebrospinal fluid from rhesus macaques (Macaca mulatta) with cisterna magna ports: Update on refinements. Comparative Medicine 72(1), 45-49.

More than 20 y ago, we developed an animal model for chronic and continuous collection of cerebrospinal fluid (CSF) from conscious rhesus macaques. Since our previous publication in 2003, we have successfully implanted 168 rhesus...

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...

Kulyar, M. F.-A., Ashfaq, K., Aqib, A. I. et al. 2022. Enhanced healing activity of manuka honey and nitrofurazone composite in full-thickness burn wounds in the rabbit model. Frontiers in Veterinary Science 9, 875629.

Burns cause many significant changes in metabolism and inflammatory reactions, leading to poor regeneration in animals and humans. A list of medicines to treat burns is available in the market. But due to the high...

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...

Álvarez, E. R., Solé, L. V., Mateo, A. G. de C. 2022. Comparison of subcutaneous sedation with alfaxalone or alfaxalone-midazolam in pet guinea pigs (Cavia porcellus) of three different age groups. Journal of the American Veterinary Medical Association 260(9), 1024–1030.

OBJECTIVE To compare the cardiorespiratory effects, quality and duration of sedation of 2 subcutaneous sedation protocols for noninvasive procedures in guinea pigs (GPs). ANIMALS 24 pet GPs (15 females, 9 males) of 3 different age...

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...

Stow, R., Kendrick, J., Ibbotson, N. et al. 2021. A new group housing approach for non-human primate metabolism studies. Journal of Pharmacological and Toxicological Methods 107, 106947.

Understanding the absorption, distribution, metabolism and excretion (ADME) of candidate drugs in preclinical species is an integral part of the safety and efficacy evaluation in drug development. For this purpose, the housing of single animals...

Argüelles, J., Echaniz, M., Bowen, J. et al. 2021. The impact of a stress-reducing protocol on the quality of pre-anaesthesia in cats. Veterinary Record 188(12), e138.

Introduction: Transport to the clinic is a major source of stress for cats. The process involves being put into a carrier, driven in a car and handled. Cats are therefore removed from the safe-haven of...

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...

Prior, H., Blunt, H., Crossman, L. et al. 2021. Refining procedures within regulatory toxicology studies: Improving animal welfare and data. Animals 11(11), 3057.

During the development of potential new medicines or agrochemicals, an assessment of the safety profile to humans and environmental species is conducted using a range of different in silico and in vitro techniques in conjunction...

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...

Botman, J., Hontoir, F., Gustin, P. et al. 2020. Postanaesthetic effects of ketamine–midazolam and ketamine–medetomidine on gastrointestinal transit time in rabbits anaesthetised with isoflurane. Veterinary Record 186(8), 249.

Gastrointestinal stasis is a common perianaesthetic complication in rabbits. The objective of this study was to assess the impact on gastrointestinal transit time of ketamine–midazolam (KMZ) versus ketamine–medetomidine (later antagonised by atipamezole) (KMT-A) in rabbits...

Yaw, T. J., Mans, C., Johnson,S. et al. 2020. Evaluation of subcutaneous administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius). Journal of the American Veterinary Medical Association 256(5), 573-579.

OBJECTIVE: To evaluate SC administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius). ANIMALS: 12 healthy juvenile ball pythons. PROCEDURES: In a randomized crossover study, each snake was administered a combination of...

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...

Lawrence, M. J., Raby, G. D., Teffer, A. K. et al. 2020. Best practices for non-lethal blood sampling of fish via the caudal vasculature. Journal of Fish Biology 97(1), 4–15.

Blood sampling through the caudal vasculature is a widely used technique in fish biology for investigating organismal health and physiology. In live fishes, it can provide a quick, easy and relatively non‐invasive method for obtaining...