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...

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...

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...

Vis, A., Lammers, J. C. A. M., de Vroege, R. et al. 2021. Strategies to improve survival from surgery for heart valve implantation in sheep. Comparative Medicine 71(3), 235-239.

Sheep are a commonly used and validated model for cardiovascular research and, more specifically, for heart valve research. Implanting a heart valve on the arrested heart in sheep is complex and is often complicated by...

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...

Hausmann, J. C., Krisp, A. R., Mans, C. et al. 2021. Analgesic efficacy of tramadol and morphine in White's tree frogs (Litoria caerulea). JAALAS 60(6), 681-686.

Published data are sparse regarding the recognition of clinically relevant pain and appropriate analgesia in amphibians. The amphibian analgesia literature has primarily focused on nociceptive pathways in a single species, the northern leopard frog (Rana...

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...

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...

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...

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...

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)...

Bellini, L., De Benedictis, G. M. 2019. Effect of three opioid-based analgesic protocols on the perioperative autonomic-mediated cardiovascular response in sheep. Laboratory Animals 53(5), 491–499.

Few reports evaluate the clinical effects of opioids in sheep during experimental surgical procedures. Catecholamine-mediated haemodynamic changes resulting from surgical noxious stimulation are blunted by opioids. The aim of this study was to evaluate the...

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...

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...

Stillman, M. W., Whittaker, A. L. 2019. Use and efficacy of analgesic agents in sheep (Ovis aries) used in biomedical research. JAALAS 58(6), 755–766.

Sheep (Ovis aries) are widely used as large animal models in biomedical research. However, current literature on the use of analgesics in sheep generally focuses on an industry or farm level of use. This structured...

Morrison, K.E., Strahl-Heldreth, D. Clark-Price, S.C. 2016. Isoflurane, sevoflurane and desflurane use in cane toads (Rhinella marina). Veterinary Record Open 3(1), e000185.

Anaesthetic chamber concentrations of isoflurane, sevoflurane and desflurane that resulted in loss of righting reflex within 15 minutes in 50 per cent of toads (Rhinella marina) exposed (ED50-LRR

Wolfensohn, S., Hawkins, P., Lilley, E. et al. 2013. Reducing suffering in experimental autoimmune encephalomyelitis (EAE). Journal of Pharmacological and Toxicological Methods 67(3), 169-176.

This report is based on discussions and submissions from an expert working group consisting of veterinarians, animal care staff and scientists with expert knowledge relevant to the field. It aims to facilitate the implementation of...