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...

Eeza, M. N. H., Singer, R., Ding, Y. et al. 2023. Probing microstructural changes in muscles of leptin-deficient zebrafish by non-invasive ex-vivo magnetic resonance microimaging. PLOS ONE 18(4), e0284215.

Leptin is a hormone that plays a key role in controlling food intake and energy homeostasis. Skeletal muscle is an important target for leptin and recent studies have shown that leptin deficiency may lead to...

Flores Dueñas, C. A., Cordero Yañez, I. A., González, R. M. et al. 2023. Translational echocardiography: The dog as a clinical research model of cardiac dysfunction. Applied Sciences 13(7), 4437.

Heart disease is a major contributor to mortality and disability on a global scale. Hence, there is a need for research to improve non-invasive diagnostic techniques. Diseases in dogs with characteristics very similar to those...

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...

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...

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...

Archibald, W., Glynn, C. 2021. Refining cages for social housing of non-human primates on ADME studies. Animal Technology and Welfare 20(2), 172-174.

The assessment and understanding of Absorption, Distribution, Metabolism and Elimination (ADME) for new pharmaceuticals is required in regulatory submissions. Typically, ADME studies are conducted using metabolism cages designed for the single housing of animals to...

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...

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...

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...

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)...

Goodroe, A., Fitz, C., Bakker, J. 2020. Current topics in marmoset anesthesia and analgesia. ILAR Journal 61(2-3), 218-229.

Anesthetic and analgesics are essential components of both clinical and research procedures completed in marmosets. A review of current anesthetic and analgesic regimens for marmosets has been complied to provide a concise reference for veterinarians...

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...

Jones, C. T., Fransson, B. A. 2019. Evaluation of the effectiveness of preoperative administration of maropitant citrate and metoclopramide hydrochloride in preventing postoperative clinical gastroesophageal reflux in dogs. Journal of the American Veterinary Medical Association 255(4), 437-445.

OBJECTIVE To investigate the prophylactic effectiveness of preoperative administration of maropitant citrate and metoclopramide hydrochloride in preventing postoperative clinical gastroesophageal reflux (GER) in dogs and to identify risk factors for clinical postoperative GER in dogs...

Gill, S. S., Buote, N. J., Peterson, N. W. et al. 2019. Factors associated with dehiscence and mortality rates following gastrointestinal surgery in dogs. Journal of the American Veterinary Medical Association 255(5), 569-573.

OBJECTIVE To identify factors associated with dehiscence and mortality rates following gastrointestinal surgery in dogs. ANIMALS 170 client-owned dogs that underwent gastrointestinal surgery from 2010 to 2016. PROCEDURES Medical records of all included dogs were...

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...

Lucrezia Costa, G., Nastasi, B., Spadola, F. et al. 2019. Effect of levobupivacaine, administered intraperitoneally, on physiological variables and on intrasurgery and postsurgery pain in dogs undergoing ovariohysterectomy. Journal of Veterinary Behavior 30, 33-36.

The aim of this study was to evaluate intraoperative and postoperative efficacy and cardiovascular effects of levobupivacaine compared with bupivacaine, administered intraperitoneally in dogs undergoing ovariohysterectomy surgery. Thirty female dogs were divided into three groups...

Collymore, C., Kent, L., Ahn, S. K. et al. 2018. Humane endpoints for guinea pigs used for Mycobacterium tuberculosis vaccine research. Comparative Medicine 68(1), 41–47.

Guinea pigs are a commonly used model for tuberculosis vaccine research. Loss of body weight is the most frequently described humane endpoint for animals used in these studies. During a chronic study, we noted labored...

Regan, D., Garcia, K., Thamm, D. 2018. Clinical, pathological, and ethical considerations for the conduct of clinical trials in dogs with naturally occurring cancer: A comparative approach to accelerate translational drug development. ILAR Journal 59(1), 99-110.

The role of comparative oncology in translational research is receiving increasing attention from drug developers and the greater biomedical research community. Pet dogs with spontaneous cancer are important and underutilized translational models, owing to dogs’...

Deckers, N., Ruigrok, C. A., Verhoeve, H. P. et al. 2018. Comparison of pain response after subcutaneous injection of two maropitant formulations to beagle dogs. Veterinary Record Open 5(1), e000262.

The antiemetic maropitant, with metacresol as preservative (Cerenia, Zoetis), has been associated with pain after subcutaneous injection in dogs and cats. Recently, a generic formulation containing benzyl alcohol was authorised (Prevomax, Le Vet). Benzyl alcohol...

Schmitz, S., Tacke, S., Guth, B. et al. 2017. Repeated anaesthesia with isoflurane and medetomidine-midazolam-fentanyl in guinea pigs and its influence on physiological parameters. PLOS ONE 12(3), e0174423.

Repeated anaesthesia may be required in experimental protocols and in daily veterinary practice, but anaesthesia is known to alter physiological parameters in GPs (Cavia porcellus, GPs). This study investigated the effects of repeated anaesthesia with...

Miranda, A., Pego, J. M., Correia-Pinto, J. 2017. Animal facility videoendoscopic intubation station: Tips and tricks from mice to rabbits. Laboratory Animals 51(2), 204-207.

Endotracheal intubation of laboratory animals is a common procedure shared by several research fields for different purposes, such as mechanical ventilation of anaesthetized animals, instillation of cytotoxic nanoparticles, infectious agents or tumour cells for induction...