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...

Robinson, L. M., Weiss, A. (Eds.) 2023. Nonhuman Primate Welfare: From History, Science, and Ethics to Practice. Springer, Cham, Switzerland. 671 p.

This volume reviews the broad topic of welfare in nonhuman primates under human care. Chapters detail the history of primates in captivity, ethical and legal issues surrounding the use of nonhuman primates as entertainment or...

Bozzay, J. D., Walker, P. F., Atwood, R. E. et al. 2023. Development, refinement, and characterization of a nonhuman primate critical care environment. PLOS ONE 18(3), e0281548.

Systemic inflammatory response remains a poorly understood cause of morbidity and mortality after traumatic injury. Recent nonhuman primate (NHP) trauma models have been used to characterize the systemic response to trauma, but none have incorporated...

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...

Attokaren, M. K., Jeong, N., Blanpain, L. et al. 2023. BrainWAVE: A flexible method for noninvasive stimulation of brain rhythms across species. ENeuro 10(2) ENEURO.0257-22.2022.

Rhythmic neural activity, which coordinates brain regions and neurons to achieve multiple brain functions, is impaired in many diseases. Despite the therapeutic potential of driving brain rhythms, methods to noninvasively target deep brain regions are...

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...

Rogers, L. J. 2023. Knowledge of lateralized brain function can contribute to animal welfare. Frontiers in Veterinary Science 10.

The specialized functions of each hemisphere of the vertebrate brain are summarized together with the current evidence of lateralized behavior in farm and companion animals, as shown by the eye or ear used to attend...

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...

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...

Elane, G. L., Portela, D. A., Hobbs, K. J. et al. 2023. Sedated cesarean sections are associated with increased kid survival compared to general anesthesia in goats: Retrospective cohort of 45 cases (2011–2021). Journal of the American Veterinary Medical Association 261(3), 391–396.

OBJECTIVE To determine whether anesthesia type (sedation or general anesthesia) affects kid survival to discharge in caprine cesarean sections (C-sections). ANIMALS Retrospective cohort of 99 caprine C-sections (2011–2021). PROCEDURES All surgeries were performed via left...

Martin-Flores, M., Nugen, S. A., Boesch, J. M. et al. 2023. Low-dose epidural anesthesia decreases the use of intraoperative systemic analgesics in goats undergoing lower urinary tract surgery. Journal of the American Veterinary Medical Association 261(8), 1147–1151.

OBJECTIVE To test whether the use of low-dose epidural anesthesia (EA) in goats undergoing lower urinary tract surgery reduces the requirements of perioperative analgesics, contributes to intraoperative hypotension, and improves postoperative comfort during the first...

Nyqvist, D., Schiavon, A., Candiotto, A. et al. 2023. PIT-tagging Italian spined loach (Cobitis bilineata): Methodology, survival and behavioural effects. Journal of Fish Biology 102(3), 575–580.

The Italian spined loach (Cobitis bilineata) is an elongated, small-sized (

Psarou, E., Vezoli, J., Schölvinck, M. L. et al. 2023. Modular, cement-free, customized headpost and connector-chamber implants for macaques. Journal of Neuroscience Methods 393, 109899.

Background: Neurophysiological studies with awake macaques typically require chronic cranial implants. Headpost and connector-chamber implants are used to allow head stabilization and to house connectors of chronically implanted electrodes, respectively. New method: We present long-lasting...

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...

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...

Knaebe, B., Weiss, C. C., Zimmermann, J. et al. 2022. The promise of behavioral tracking systems for advancing primate animal welfare. Animals 12(13), 1648.

Recent years have witnessed major advances in the ability of computerized systems to track the positions of animals as they move through large and unconstrained environments. These systems have so far been a great boon...

Marques Maia, C., Volpato, G. L., Braithwaite, V. A. 2022. A psychological aversive condition does not change individual zebrafish preference for background color or artificial plant enrichments. Journal of Applied Animal Welfare Science 25(4), 427-438.

Information on fish preference for environmental conditions can be a useful tool to offer them what they want, an important requirement for welfare purposes. Giving that such an approach deals with psychological states of the...

Prentice, P. M., Houslay, T. M., Wilson, A. J. 2022. Exploiting animal personality to reduce chronic stress in captive fish populations. Frontiers in Veterinary Science 9, 1046205.

Chronic stress is a major source of welfare problems in many captive populations, including fishes. While we have long known that chronic stress effects arise from maladaptive expression of acute stress response pathways, predicting where...

Serrano, C., Antonio, J. 2022. Ultrasound guided surgery as a refinement tool in oncology research. Animals 12(23), 3445.

Refinement is one of the ethical pillars of the use of animals in research. Ultrasonography is currently used in human medicine as a surgical tool for guided biopsies and this idea can be applied to...

Torgerson-White, L., Sánchez-Suárez, W. 2022. Looking beyond the shoal: Fish welfare as an individual attribute. Animals 12(19), 2592.

Welfare is an individual attribute. In general, providing captive nonhuman animals with conditions conducive to good welfare is an idea more easily applied when dealing with few individuals. However, this becomes much harder—if not impossible—under...

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...

Robinson, L. M., Waran, N. K., Handel, I. et al. 2021. Happiness, welfare, and personality in rhesus macaques (Macaca mulatta). Applied Animal Behaviour Science 236, 105268.

When we treat an animal’s welfare as an individual experience, we should consider the possibility that it may be associated with individual differences in personality. We tested for such associations in 44 socially housed rhesus...

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...

Fife-Cook, I., Franks, B. 2021. Koi (Cyprinus rubrofuscus) seek out tactile interaction with humans: General patterns and individual differences. Animals 11(3), 706.

The study of human–animal interactions has provided insights into the welfare of many species. To date, however, research has largely focused on human relationships with captive mammals, with relatively little exploration of interactions between humans...