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. 
Farag, A., Mandour, A. S., Hendawy, H. et al. 2023. A review on experimental surgical models and anesthetic protocols of heart failure in rats. Frontiers in Veterinary Science 10, 1103229.

Heart failure (HF) is a serious health and economic burden worldwide, and its prevalence is continuously increasing. Current medications effectively moderate the progression of symptoms, and there is a need for novel preventative and reparative...

Malik, A., Zavadil, J. A., Geusz, M. E. 2023. Using bioluminescence to image gene expression and spontaneous behavior in freely moving mice. PLOS ONE 18(1), e0279875.

Bioluminescence imaging (BLI) of gene expression in live animals is a powerful method for monitoring development, tumor growth, infections, healing, and other progressive, long-term biological processes. BLI remains an effective approach for reducing the number...

Palumbo, G., Kunze, L. H., Oos, R. et al. 2023. Longitudinal studies on Alzheimer disease mouse models with multiple tracer PET/CT: Application of reduction and refinement principles in daily practice to safeguard animal welfare during progressive aging. Animals 13(11), 1812.

Longitudinal studies on mouse models related to Alzheimer disease (AD) pathology play an important role in the investigation of therapeutic targets to help pharmaceutical research in the development of new drugs and in the attempt...

McKinney, M. M., Dupont, W. D., Corson, K. J. et al. 2022. Physiologic and behavioral effects in mice anesthetized with isoflurane in a red-tinted or a traditional translucent chamber. JAALAS 61(4), 322-332.

Isoflurane has been characterized as a distressing agent for rodents, causing both physiologic and behavioral effects. Using a "darkened home cage" has been recommended during CO2 administration for rodent euthanasia; this is arguably a similar...

Chen, T., Zhou, Z.-Y., Liu, J.-Y. et al. 2022. Impact of partial bile duct ligation with or without repeated magnetic resonance imaging examinations in mice. Scientific Reports 12(1), 21014.

Partial bile duct ligation (pBDL) is considered a well-tolerated cholestatic model. Magnetic resonance imaging (MRI) is one of the most widely used tools in noninvasive imaging. However, no systematic studies have reported the possible effects...

Farag, A., Mandour, A. S., Hamabe, L. et al. 2022. Novel protocol to establish the myocardial infarction model in rats using a combination of medetomidine-midazolam-butorphanol (MMB) and atipamezole. Frontiers in Veterinary Science 9, 1064836.

Myocardial infarction (MI) is one of the most common cardiac problems causing deaths in humans. Previously validated anesthetic agents used in MI model establishment are currently controversial with severe restrictions because of ethical concerns. The...

Navarro, K. L., Huss, M., Smith, J. C. et al. 2021. Mouse anesthesia: The art and science. ILAR Journal 62(1-2), 238-273.

There is an art and science to performing mouse anesthesia, which is a significant component to animal research. Frequently, anesthesia is one vital step of many over the course of a research project spanning weeks...

Blevins, C. E., Celeste, N. A., Marx, J. O. 2021. Effects of oxygen supplementation on injectable and inhalant anesthesia in C57BL/6 mice. JAALAS 60(3), 289-297.

Oxygen supplementation is rarely considered when anesthetizing laboratory mice, despite reports that mice become profoundly hypoxic under anesthesia. Little is known about the effects of hypoxia on anesthetic performance. This article focuses on the effects...

Alemán-Laporte, J., Bandini, L. A., Garcia-Gomes, M. S. et al. 2020. Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization. Laboratory Animals 54(2), 171–182.

In this study, the effect of four anaesthetic protocols that included the combination of xylazine (X) and ketamine (K) with acepromazine (A) and opioids (methadone (Me), morphine (Mo) or tramadol (T)) was evaluated in laboratory...

Ballantine, A., Rodgers, D., Watts, C. et al. 2020. The cotton rat – a new challenge. Animal Technology and Welfare 19(1), 92-95.

This poster describes how the Animal Technologists at Envigo adapted their current practices and procedures for a new species at their laboratory: the cotton rat. The paper describes cotton rat biology and behaviour; housing; environmental...

Gjendal, K., Ottesen, J. L., Olsson, I. et al. 2020. Effect of repeated exposure to isoflurane on nest building and burrowing in mice. JAALAS 59(1), 30–36.

Nest building and burrowing are highly motivated natural behaviors in rodents, and changes in these behaviors can serve as welfare assessment tools. In this study, we investigated: 1) the limits of agreement between 2 observers...

Kersemans, V., Wallington, S., Allen, P. D. et al. 2020. Manganese-free chow, a refined non-invasive solution to reduce gastrointestinal signal for T1-weighted magnetic resonance imaging of the mouse abdomen. Laboratory Animals 54(4), 353–364.

Commercial mouse chow is designed to provide a complete, nutrient-rich diet, and it can contain upwards of 100 mg/kg manganese, an essential mineral. Manganese acts as a relaxation time-shortening contrast agent for both T1 and T2...

Tang, W., Zillmann, U., Sprengel, R. 2020. Alternative anesthesia of neonatal mice for global rAAV delivery in the brain with non-detectable behavioral interference in adults. Frontiers in Behavioral Neuroscience 14, 115.

Viral-transduced gene expression is the current standard for cell-type-specific labeling and cell tacking in experimental neuroscience. To achieve widespread gene expression, a viral delivery method to neonatal rodents was introduced more than two decades ago...

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...

Gergye, C. H., Zhao, Y., Moore, R. et al. 2020. A comparison of ketamine or etomidate combined with xylazine for intraperitoneal anesthesia in four mouse strains. JAALAS 59(5), 519-530.

Intraperitoneal (IP) injection is a common route of anesthetic administration in mice. Ketamine-xylazine (KX) anesthesia is one of the most widely used IP protocols, but has limitations. Etomidate is an alternative to ketamine that has...

West, S. E., Lee, J. C., Johns, T. N. et al. 2020. Intraperitoneal alfaxalone and alfaxalone–dexmedetomidine anesthesia in Sprague–Dawley rats (Rattus norvegicus). JAALAS 59(5), 531-538.

Due to their unpredictability and variable effects, injectable anesthetic regimens in laboratory rodent species warrant refinement. In our study we sought to evaluate alfaxalone, which has gained recent popularity in veterinary medicine, alone and in...

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...

Klune, C. B., Robbins, H. N. K., Leung, V. et al. 2020. Hypothermia during general anesthesia interferes with pain assessment in laboratory rats (Rattus norvegicus). JAALAS 59(6), 719-725.

Accurate pain assessment methods are necessary to ensure animal welfare and reliable data collection in animal research. The Rat Grimace Scale (RGS), a facial expression pain scale, allows effective identification of pain. However, the potential...

Ho, H., Fowle, A., Coetzee, M. et al. 2020. An inhalation anaesthesia approach for neonatal mice allowing streamlined stereotactic injection in the brain. Journal of Neuroscience Methods 342, 108824.

Background: Investigating brain function requires tools and techniques to visualise, modify and manipulate neuronal tissue. One powerful and popular method is intracerebral injection of customised viruses, allowing expression of exogenous transgenes. This technique is a...

Stevens, C., Hawkins, P., Lovell-Badge, R. et al. 2019. Report of the 2018 RSPCA/UFAW Rodent and Rabbit Welfare Group meeting. Animal Technology and Welfare 18(2), 81-91.

The RSPCA/UFAW Rodent (and now Rabbit) Working Group has held a one-day meeting every autumn for the last 25 years, so that its members can discuss current welfare research, exchange views on welfare issues and...

Erickson, R. L., Blevins, C. E., De Souza Dyer, C. et al. 2019. Alfaxalone-xylazine anesthesia in laboratory mice (Mus musculus). JAALAS 58(1), 30-39.

Since its recent reformulation, alfaxalone has gained popularity as an injectable veterinary anesthetic, including promising studies demonstrating the use of alfaxalone-xylazine for anesthesia in mice. Here we sought to expand these studies by testing additional...

Jiron, J. M., Mendieta Calle, J. L., Castillo, E. J. et al. 2019. Comparison of isoflurane, ketamine-dexmedetomidine, and ketamine-xylazine for general anesthesia during oral procedures in rice rats (Oryzomys palustris). JAALAS 58(1), 40-49.

Rice rats (Oryzomys palustris) are an unconventional laboratory species that has been used to study photoperiodicity, periodontitis, and osteonecrosis of the jaw. Interventional procedures that require anesthesia, including oral procedures, are sometimes necessary in preclinical...

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...

Bauer, C., Schillinger, U., Brandl, J. et al. 2019. Comparison of pre-emptive butorphanol or metamizole with ketamine +medetomidine and s-ketamine + medetomidine anaesthesia in improving intraoperative analgesia in mice. Laboratory Animals 53(5), 459–469.

In accordance with the ‘refinement’ component of the 3Rs, the primary aim of this study was to investigate and compare ketamine + medetomidine (KM) and s-ketamine + medetomidine (SKM) anaesthetic protocols in C57BL/6J mice (both sexes). We sought to...