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. 
Hedenqvist, P., Trbakovic, A., Mellgren, T. et al. 2020. The effect of housing environment on bone healing in a critical radius defect in New Zealand white rabbits. PLOS ONE 15(5), e0233530.

In animal studies on bone healing, the effect of housing space and physical activity are seldom taken into account. Bone formation was evaluated in New Zealand White rabbits (mean ± SEM BW: 3.9 ± 0.11...

Zhang, X., Kumstel, S., Tang, G. et al. 2020. A rational approach of early humane endpoint determination in a murine model for cholestasis. ALTEX 37(2), 197-207.

Reduction of animal suffering during in vivo experiments is usually ensured by continuously monitoring the health status using a score sheet and by applying humane endpoints. However, most studies do not evaluate the plausibility of...

Turner, P. V., Hickman, D. L., van Luijk, J. et al. 2020. Welfare impact of carbon dioxide euthanasia on laboratory mice and rats: A systematic review. Frontiers in Veterinary Science 7, 411.

Background: There has been increased concern about the suitability of CO2 as a method for euthanasia of laboratory mice and rats, including the potential discomfort, pain or distress that animals may experience prior to loss...

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...

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...

Singleton, S., Nefla, M., Dennison, N. et al. 2020. Assessing pain in models of rheumatoid arthritis. Animal Technology and Welfare 19(2), 149-152.

A hallmark symptom of rheumatoid arthritis in humans is painful swollen joints. Pain can manifest before any inflammation is noticeable as well as persist long after inflammation has resolved. In rodent models of arthritis, ankle...

Shomer, N. H., Allen-Worthington, K. H., Hickman, D. L. et al. 2020. Review of rodent euthanasia methods. JAALAS 59(3), 242–253.

The optimal choice of euthanasia method for laboratory rodents depends on a number of factors, including the scientific goals of the study, the need to minimize animal pain and/or distress, applicable guidelines and laws, the...

Laferriere, C. A., Pang, D. S. 2020. Review of intraperitoneal injection of sodium pentobarbital as a method of euthanasia in laboratory rodents. JAALAS 59(3), 254–263.

Euthanasia is one of the most commonly performed procedures in biomedical research, involving tens of millions of animals in North America and Europe every year. The use of sodium pentobarbital, injected intraperitoneally, for killing rodents...

Laferriere, C. A., Leung, V. S., Pang, D. S. 2020. Evaluating intrahepatic and intraperitoneal sodium pentobarbital or ethanol for mouse euthanasia. JAALAS 59(3), 264–268.

Intraperitoneal (IP) injection of sodium pentobarbital (PB) is an accepted method of euthanasia for mice. However, this method has important drawbacks, including the potential for pain or misinjection. The objective of this prospective, randomized, blinded...

Rix, A., Drude, N., Mrugalla, A. et al. 2020. Performance of severity parameters to detect chemotherapy-induced pain and distress in mice. Laboratory Animals 54(5), 452-460.

According to European Union directive 2010/63/EU a severity classification of experimental procedures performed on laboratory animals is mandatory. This includes a prospective evaluation of all interventions performed within the experiment, as well as an assessment...

Cloutier Barbour, C., Danforth, M. D., Murphy, H. et al. 2020. Monitoring great ape heart health through innovative electrocardiogram technology: Training methodologies and welfare implications. Zoo Biology 39(6), 443-447.

Assessing and treating cardiovascular disease (or heart disease) is a growing concern for institutions housing great apes, as it is a major cause of mortality in all four taxa managed in human care. As part...

Natusch, D. J. D., Aust, P. W., Khadiejah, S. et al. 2020. Behavioral and corticosterone responses to carbon dioxide exposure in reptiles. PLOS ONE 15(10), e0240176.

The use of carbon dioxide (CO2) exposure as a means of animal euthanasia has received considerable attention in mammals and birds but remains virtually untested in reptiles. We measured the behavioral responses of four squamate...

Tang, G., Seume, N., Häger, C. et al. 2020. Comparing distress of mouse models for liver damage. Scientific Reports 10(1), 19814.

In order to foster animal welfare as well as high quality of research, many countries regulate by law that the severity of animal experiments must be evaluated and considered when performing biomedical research. It is...

van der Vinne, V., Pothecary, C. A., Wilcox, S. L. et al. 2020. Continuous and non-invasive thermography of mouse skin accurately describes core body temperature patterns, but not absolute core temperature. Scientific Reports 10(1), 20680.

Body temperature is an important physiological parameter in many studies of laboratory mice. Continuous assessment of body temperature has traditionally required surgical implantation of a telemeter, but this invasive procedure adversely impacts animal welfare. Near-infrared...

Elmi, A., Galligioni, V., Govoni, N. et al. 2020. Quantification of hair corticosterone, DHEA and testosterone as a potential tool for welfare assessment in male laboratory mice. Animals 10(12), 2408.

Steroids, providing information regarding several biological patterns including stress and sexual behavior, have been investigated in different matrices in laboratory mice. Data regarding hair quantification, indicative of longer timespans when compared to blood and saliva...

Felgenhauer, J. L., Brune, J. E., Long, M. E. et al. 2020. Evaluation of nutritional gel supplementation in C57BL/6J mice infected with mouse-adapted Influenza A/PR/8/34 virus. Comparative Medicine 70(6), 471-486.

Mice are a common animal model for the study of influenza virus A (IAV). IAV infection causes weight loss due to anorexia and dehydration, which can result in early removal of mice from a study...

Do, J. P., Defensor, E. B., Ichim, C. V. et al. 2020. Automated and continuous monitoring of animal welfare through digital alerting. Comparative Medicine 70(4), 313-327.

A primary goal in preclinical animal research is respectful and responsible care aimed toward minimizing stress and discomfort while enhancing collection of accurate and reproducible scientific data. Researchers use hands-on clinical observations and measurements as...

Scarborough, J., Mueller, F., Arban, R. et al. 2020. Preclinical validation of the micropipette-guided drug administration (MDA) method in the maternal immune activation model of neurodevelopmental disorders. Brain, Behavior, and Immunity 88, 461-470.

Pharmacological treatments in laboratory rodents remain a cornerstone of preclinical psychopharmacological research and drug development. There are numerous ways in which acute or chronic pharmacological treatments can be implemented, with each method having certain advantages...

Kloefkorn H, Aiani, L. M., Lakhani, A. et al. 2020. Noninvasive three-state sleep-wake staging in mice using electric field sensors. Journal of Neuroscience Methods 344, 108834.

Study Objective: Validate a novel method for sleep-wake staging in mice using noninvasive electric field (EF) sensors. Methods: Mice were implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes and housed individually. Noninvasive EF sensors were...

Woodard, C. L., Nasrallah, W. B., Samiei, B. V. et al. 2020. PiDose: An open-source system for accurate and automated oral drug administration to group-housed mice. Scientific Reports 10, 11584.

Drug treatment studies in laboratory mice typically employ manual administration methods such as injection or gavage, which can be time-consuming to perform over long periods and cause substantial stress in animals. These stress responses may...

X. Hui, Kan, E. C. 2019. No-touch measurements of vital signs in small conscious animals. Science Advances 5, eaau0169.

Measuring the heartbeat and respiration of small conscious animals is important for assessing their health and behavior, but present techniques such as electrocardiogram (ECG), ultrasound, and auscultation rely on close skin contact with the animal...

Axiak Flammer, S., Eskes, C., Kohler, I. et al. 2019. Alternatives to carbon dioxide—Taking responsibility for humanely ending the life of animals. Animals 9(8), 482.

Carbon dioxide (CO2) is commonly used to kill rodents. However, a large body of research has now established that CO2 is aversive to them. A multidisciplinary symposium organized by the Swiss Federal Food Safety and...

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...

Steiner, A. R., Axiak Flammer, S., Beausoleil, N. J. et al. 2019. Humanely ending the life of animals: Research priorities to identify alternatives to carbon dioxide. Animals 9(11), 911.

The use of carbon dioxide (CO2) for stunning and killing animals is considered to compromise welfare due to air hunger, anxiety, fear, and pain. Despite decades of research, no alternatives have so far been found...

Adams, R., Stanley, C. E., Piana, E. et al. 2019. Physiological and behavioral indicators to measure crustacean welfare. Animals 9(11), 914.

The purpose of this project was to determine how neural circuits were affected during warming by examining sensory neurons, the neuromuscular junction, and the cardiac function and behavior of the commercially important crustacean species, the...