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...

Sen Sarma, O., Frymus, N., Axling, F. et al. 2023. Optimizing zebrafish rearing−Effects of fish density and environmental enrichment. Frontiers in Behavioral Neuroscience 17, 1204021.

Despite its popularity in research, there is very little scientifically validated knowledge about the best practices on zebrafish (Danio rerio) husbandry, which has led to several facilities having their own husbandry protocols. This study was...

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...

Saraiva, J. L., Rachinas-Lopes, P., Arechavala-Lopez, P. 2022. Finding the “golden stocking density”: A balance between fish welfare and farmers’ perspectives. Frontiers in Veterinary Science 9, 930221.

The effects of stocking density on fish welfare are complex and involve many interacting parameters. This complex relationship between fish welfare, stocking density and influencing factors make it challenging to define a specific optimal (“golden”)...

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...

Martini, A., Huysseune, A., Witten, P. E. et al. 2021. Plasticity of the skeleton and skeletal deformities in zebrafish (Danio rerio) linked to rearing density. Journal of Fish Biology 98(4), 971-986.

The teleost zebrafish (Danio rerio), an established model for human skeletal diseases, is reared under controlled conditions with defined parameters for temperature and photoperiod. Studies aimed at defining the proper rearing density have been performed...

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...

Andersson, M., Kettunen, P. 2021. Effects of holding density on the welfare of zebrafish: A systematic review. Zebrafish 18(5), 297-306.

The zebrafish is becoming an increasingly popular research animal around the world. Its welfare is affected by an array of environmental factors, such as food access and water quality. Holding density is an important welfare...

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...

Rasys, A. M., Divers, S. J., Lauderdale, J. D. et al. 2020. A systematic study of injectable anesthetic agents in the brown anole lizard (Anolis sagrei). Laboratory Animals 54(3), 281–292.

Anolis lizards have served as important research models in fields ranging from evolution and ecology to physiology and biomechanics. However, anoles are also emerging as important models for studies of embryo development and tissue regeneration...

Kane, L. P., Chinnadurai, S. K., Vivirito, K. et al. 2020. Comparison of isoflurane, sevoflurane, and desflurane as inhalant anesthetics in prairie rattlesnakes (Crotalus viridis). Journal of the American Veterinary Medical Association 257(9), 945-949.

OBJECTIVE: To characterize induction and recovery characteristics of 3 commonly used inhalant anesthetics in prairie rattlesnakes (Crotalus viridis): isoflurane, sevoflurane, and desflurane. ANIMALS: 12 healthy adult prairie rattlesnakes. PROCEDURES: In a randomized crossover design, snakes...

Kane, L. P., Chinnadurai, S. K., Vivirito, K. et al. 2020. Comparison of isoflurane, sevoflurane, and desflurane as inhalant anesthetics in prairie rattlesnakes (Crotalus viridis). Journal of the American Veterinary Medical Association 257(9), 945-949.

OBJECTIVE: To characterize induction and recovery characteristics of 3 commonly used inhalant anesthetics in prairie rattlesnakes (Crotalus viridis): isoflurane, sevoflurane, and desflurane. ANIMALS: 12 healthy adult prairie rattlesnakes. PROCEDURES: In a randomized crossover design, snakes...

Eshar, D., Beaufrère, H. 2020. Anesthetic effects of alfaxalone–ketamine, alfaxalone–ketamine–dexmedetomidine, and alfaxalone–butorphanol–midazolam administered intramuscularly in five striped palm squirrels (Funambulus pennantii). JAALAS 59(4), 384-392.

Injectable anesthesia protocols for five striped palm squirrels (Funambulus pennantii) are poorly described in the literature. In this study, male intact squirrels received intramuscular injections of either alfaxalone (6 mg/kg) and ketamine (40 mg/ kg...

Ambar, N., Eshar, D., Shrader, T. C. et al. 2020. Anesthetic effects of intramuscular alfaxalone–ketamine in naked mole rats (Heterocephalus glaber). JAALAS 59(5), 539-545.

In this study, adult intact male and female (n = 10) naked mole rats (Heterocephalus glaber) were anesthetized by using a combination of ketamine (20 mg/kg IM), and alfaxalone (4.0 mg/kg IM). Induction and recovery...

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)...

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-...

Browning, G. R., Eshar, D., Beaufrere, H. 2019. Comparison of dexmedetomidine-ketamine-midazolam and isoflurane for anesthesia of black-tailed prairie dogs (Cynomys ludovicianus). JAALAS 58(1), 50-57.

Few studies evaluate anesthesia in black-tailed prairie dogs (Cynomys ludovicianus). Isoflurane inhalant anesthesia is used in this species most commonly, but injectable protocols are poorly described. Here we compared the physiologic effects, including anesthetic depth...

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...

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...

Bressan, T. F., Sobreira, T., Carregaro, A. B. 2019. Use of rodent sedation tests to evaluate midazolam and flumazenil in green iguanas (Iguana iguana). JAALAS 58(6), 810–816.

This study aimed to evaluate the applicability of rodent behavioral tests to assess the effects of midazolam and flumazenil in green iguanas. Four tests commonly used to assess sedation in rodents—the open field test, forced...

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...