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...

Kaiser, S., Korte, A., Wistuba, J. et al. 2023. Effects of castration and sterilization on baseline and response levels of cortisol—A case study in male guinea pigs. Frontiers in Veterinary Science 9, 1093157.

An uncontrolled reproduction of animals in human hands should be avoided. To meet this goal, animals are widely castrated, i.e., the gonads are completely removed. Since the gonads are the most important source of sex...

Cameron, A. S., Rub, A. M. W., Sandford, B. P. 2023. Evaluation of healing progression at surgical incision sites and the use of antiseptics for enhancing post-operative survival in subyearling Chinook salmon (Oncorhynchus tshawytscha). PLOS ONE 18(7), e0288056.

In an attempt to develop more effective surgical implantation methods for fish, surgical incisions typical of those made for implanting micro-acoustic transmitters into the peritoneal cavity were evaluated on a weekly basis for healing progression...

Klabukov, I., Shestakova, V., Krasilnikova, O. et al. 2023. Refinement of animal experiments: Replacing traumatic methods of laboratory animal marking with non-invasive alternatives. Animals 13(22), 3452.

Reliable methods for identifying rodents play an important role in ensuring the success of preclinical studies. However, animal identification remains a trivial laboratory routine that is not often discussed, despite the fact that more than...

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...

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...

Lennox, R. J., Stöger, E., Dahlmo, L. S. et al. 2022. Effects of tag type and surgery on migration of Atlantic salmon (Salmo salar) smolts. Journal of Fish Biology 101(3), 515-521.

Tagging salmon smolts to provide information about the timing of outmigration has been a common approach to monitor phenology and model the risk of encountering stressors. However, the validity of tagging has come under scrutiny...

Jang, J. Y., Liang, T., Kim, M.-K. et al. 2022. A rapid and noninvasive method that extracts polymerase chain reaction-ready genomic DNA from adult zebrafish. Zebrafish 19(4), 160-164.

Genotyping usually entails analysis of the products of polymerase chain reaction (PCR) carried out with genomic DNA (gDNA) as template, and is employed for validation of mutant or transgenic organisms. For genotyping of adult zebrafish...

Chen, J., Xu, X., Dalhaimer, P. et al. 2022. Tetra-primer amplification-refractory mutationsystem (ARMS)—PCR for genotyping mouse leptin gene mutation. Animals 12(19), 2680.

Due to spontaneous deficiency in leptin, ob/ob mice are one of the most commonly used experimental animal models in diabetes research. In this study, we reported a quick and easy-to-conduct genotyping method using tetra-primer amplification...

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...

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...

Rácz, A., Allan, B., Dwyer, T. et al. 2021. Identification of individual zebrafish (Danio rerio): A refined protocol for VIE tagging whilst considering animal welfare and the principles of the 3Rs. Animals 11(3), 616.

In aquatic ecology, studies have commonly employed a tagging technique known as visible implant elastomer (VIE). This method has not been widely adopted by the zebrafish research community and also lacks refinement with regard to...

Burn, C. C., Mazlan, N. H. B., Chancellor, N. et al. 2021. The pen is milder than the blade: Identification marking mice using ink on the tail appears more humane than ear-punching even with local anaesthetic. Animals 11(6), 1664.

Identification marking mice commonly involves ear-punching with or without anaesthetic, or tail-marking with ink. To identify which is most humane, we marked weanling male BALB/c mice using ear-punching (EP), ear-punching with anaesthetic EMLATM cream (EP+A)...

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...

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...

Young, T., Whiteside, T., Locklear, J. 2020. What is your tattoo ink telling you? Laboratory Animal Science Professional 8(2) (March/April), 62-65.

Tattooing traumatizes the skin, which can result in microbial infections with the severity ranging from minor to life-threating septicemia. Additionally, the metals in colored tattoo ink are known to cause dermal inflammation in some people...

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...

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...

Huang, J., Kayne, P. S. 2020. Buccal swab based genotyping of genetically modified mice. Laboratory Animal Science Professional 8(5) (September/October), 64-66.

Routine sample collection for genotyping genetically modified animals (rodents) (GMAs) typically includes tail snip, toe clip, or ear biopsy. To decrease the potential pain and distress caused by tissue sample collection for genetic analysis, we...

Tilley, C. A., Carreño Gutierrez, H., Sebire, M. et al. 2020. Skin swabbing is a refined technique to collect DNA from model fish species. Scientific Reports 10(1), 18212.

Model fish species such as sticklebacks and zebrafish are frequently used in studies that require DNA to be collected from live animals. This is typically achieved by fin clipping, a procedure that is simple and...

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...