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. 
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...

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...

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...

Ellis, T., Katsiadaki, I. 2021. Clarification of early end-points for refinement of animal experiments, with specific reference to fish. Laboratory Animals 55(3), 244-253.

Appropriate end-points are integral to the refinement of laboratory animal experiments. Our recent experience has highlighted that ambiguity around end-points is hampering their adoption in experiments that cause severe suffering to fish. In toxicology, the...

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...

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...

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...

Raillard, M., Detotto, C., Grepper, S. et al. 2019. Anaesthetic and perioperative management of 14 male New Zealand white rabbits for calvarial bone surgery. Animals 9(11), 896.

Calvarial bone surgery on rabbits is frequently performed. This report aims to document a simple and practical anaesthetic and perioperative management for this procedure. Fourteen male New Zealand white rabbits were included in the study...

Krall, C., Glass, S., Dancourt, G. et al. 2019. Behavioural anxiety predisposes rabbits to intra-operative apnoea and cardiorespiratory instability. Applied Animal Behaviour Science 221, 104875.

Rabbits are prone to complications from both anaesthesia and anxiety. Given that anxiety can often impact quality of anaesthesia, we developed a novel cage-side anxiety assessment, and sought to determine whether it correlated to pre-...

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...

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...

Balko, J. A., Lindemann, D. M., Allender, M. C. et al. 2019. Evaluation of the anesthetic and cardiorespiratory effects of intramuscular alfaxalone administration and isoflurane in budgerigars (Melopsittacus undulatus) and comparison with manual restraint. Journal of the American Veterinary Medical Association 254(12), 1427-1435.

OBJECTIVE To evaluate the anesthetic and cardiorespiratory effects of IM alfaxalone and isoflurane administration in budgerigars (Melopsittacus undulatus) and compare use of these agents with use of manual restraint. ANIMALS 42 healthy budgerigars. PROCEDURES For...

Dholakia, U., Seddighi, R., Odunayo, A. et al. 2019. Prolonged anesthetic recovery after continuous infusion of midazolam in 2 domestic cats (Felis catus). Comparative Medicine 69(4), 321–326.

Two healthy research cats involved in a randomized, blinded prospective pharmacodynamics study evaluating midazolam continuous-rate infusion as a means to decrease sevoflurane concentrations experienced unexpectedly prolonged recoveries. Midazolam loading doses, infusion rates, and the targeted...

Lin, C.-H., Lo, P.-Y. 2018. Simple technique for aiding thoracic CT scanning of cats without general anaesthesia. Veterinary Record 182(7), 1-3.

Thoracic CT can provide additional diagnostic information in comparison to thoracic radiography for animals with respiratory diseases; however, the requirement of general anaesthesia can be of risk and may not be possible in cats with...

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...

Wolfe, A. M., Rahman, M., McFadden, D. G. et al. 2018. Refinement and successful implementation of a scoring system for myxomatosis in a susceptible rabbit (Oryctolagus cuniculus) model. Comparative Medicine 68(4), 280–285.

Myxoma virus is a member of Leporipoxviridae whose tropism is tightly restricted to lagomorphs. In susceptible Oryctolagus rabbits, the virus causes a highly lethal disease known as myxomatosis, which begins as a localized infection but...

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...

Reupke, V., Walliser, K., Perl, T. et al. 2017. Total intravenous anaesthesia using propofol and sufentanil allows controlled long-term ventilation in rabbits without neuromuscular blocking agents. Laboratory Animals 51(3), 284-291.

The aim of this study was to evaluate a total intravenous anaesthesia (TIVA) protocol using propofol and sufentanil without neuromuscular blocking agents (NBAs) for a non-recovery lung pathology study in rabbits including 10 h of...

De Lombaert, M. C. M., Rick, E. L., Krugner-Higby, L. A. et al. 2017. Behavioral characteristics of adult zebrafish (Danio rerio) after MS222 anesthesia for fin excision. JAALAS 56(4), 377-381.

The health of laboratory animals is an ethical responsibility of researchers and a critical determinant of experimental outcome. Therefore, all Husbandry & Management procedures should be evaluated for their effects on mortality, behavior, and physiology...

Williams, M. D., Long, C. T., Durrant, J. R. et al. 2017. Oral transmucosal detomidine gel in New Zealand White rabbits (Oryctolagus cuniculus). JAALAS 56(4), 436-442.

Handling and restraining rabbits for routine procedures may be impossible without prior sedation, result in unnecessary stress or injury to the rabbit or handler, and increase experimental variability. Parenteral administration of sedatives can cause stress...

Chatigny, F., Kamunde, C., Creighton, C. M. et al. 2017. Uses and doses of local anesthetics in fish, amphibians, and reptiles. JAALAS 56(3), 244-253.

Local anesthetics are an integral part of routine pain management in mammals, yet their use is relatively limited in fish, amphibians and reptiles. These animals frequently undergo potentially painful surgical procedures and therefore could possibly...