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. 
Doucet, M. R., Laevski, A. M., Doiron, J. A. et al. 2024. Locomotor activity as an effective measure of the severity of inflammatory arthritis in a mouse model. PLOS ONE 19(1), e0291399.

Objective Mouse models are valuable in preclinical studies of inflammatory arthritis. However, current methods for measuring disease severity or responses to treatment are not optimal. In this study a smart cage system using multiple sensors...

Robinson, L. M., Weiss, A. (Eds.) 2023. Nonhuman Primate Welfare: From History, Science, and Ethics to Practice. Springer, Cham, Switzerland. 671 p.

This volume reviews the broad topic of welfare in nonhuman primates under human care. Chapters detail the history of primates in captivity, ethical and legal issues surrounding the use of nonhuman primates as entertainment or...

Ausderau, K. K., Colman, R. J., Kabakov, S. et al. 2023. Evaluating depression- and anxiety-like behaviors in non-human primates. Frontiers in Behavioral Neuroscience 16, 1006065.

Depression and anxiety are some of the most prevalent and debilitating mental health conditions in humans. They can present on their own or as co-morbidities with other disorders. Like humans, non-human primates (NHPs) can develop...

Bains, R. S., Forrest, H., Sillito, R. R. et al. 2023. Longitudinal home-cage automated assessment of climbing behavior shows sexual dimorphism and aging-related decrease in C57BL/6J healthy mice and allows early detection of motor impairment in the N171-82Q mouse model of Huntington’s disease. Frontiers in Behavioral Neuroscience 17, 1148172.

Monitoring the activity of mice within their home cage is proving to be a powerful tool for revealing subtle and early-onset phenotypes in mouse models. Video-tracking, in particular, lends itself to automated machine-learning technologies that...

Cohen, S., Ho, C. 2023. Review of rat (Rattus norvegicus), Mouse (mus musculus), Guinea pig (Cavia procellus), and rabbit (Oryctolagus cuniculus) indicators for welfare assessment. Animals 13(13), 2167.

The monitoring and assessment of animals is important for their health and welfare. The appropriate selection of multiple, validated, and feasible welfare assessment indicators is required to effectively identify compromises or improvements to animal welfare...

Liu, P., Roberts, S., Shoemaker, J. T. et al. 2023. Validation of a 3D perfused cell culture platform as a tool for humanised preclinical drug testing in breast cancer using established cell lines and patient-derived tissues. PLOS ONE 18(3), e0283044.

3D cell culture models of cancer are currently being developed to recapitulate in vivo physiological conditions and to assess therapeutic responses. However, most models failed to incorporate the biochemical and biophysical stimuli from fluid flow...

Morton, D. B. 2023. A model framework for the estimation of animal “suffering”: Its use in predicting and retrospectively assessing the impact of experiments on animals. Animals 13(5), 800.

This paper presents and illustrates, with a working example, a hypothesis for the assessment of ongoing severity before and during an experiment that will enable humane endpoints and intervention points to be applied accurately and...

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...

Peruga, M., Kawala, B., Sarul, M. et al. 2023. Are currently selected laboratory animals useful in the research of how female hormones influence orthodontic biomechanics? Animals 13(4), 629.

Animal testing was and remains the only method of introducing a certain treatment and medical procedure on humans. On the other hand, animals have their rights resulting from applicable legal acts, including Directive 2010/63/EU and...

Swan, J., Boyer, S., Westlund, K. et al. 2023. Decreased levels of discomfort in repeatedly handled mice during experimental procedures, assessed by facial expressions. Frontiers in Behavioral Neuroscience 17, 1109886.

Mice are the most commonly used laboratory animal, yet there are limited studies which investigate the effects of repeated handling on their welfare and scientific outcomes. Furthermore, simple methods to evaluate distress in mice are...

Wolter, A., Bucher, C. H., Kurmies, S. et al. 2023. A buprenorphine depot formulation provides effective sustained post-surgical analgesia for 72 h in mouse femoral fracture models. Scientific Reports 13(1), 3824.

Adequate pain management is essential for ethical and scientific reasons in animal experiments and should completely cover the period of expected pain without the need for frequent re-application. However, current depot formulations of Buprenorphine are...

O’Brien, S. L., Cronin, K. A. 2023. Doing better for understudied species: Evaluation and improvement of a species-general animal welfare assessment tool for zoos. Applied Animal Behaviour Science 264, 105965.

Accredited zoos and aquariums are required to have a welfare assessment process in place for the animals in their care. However, welfare assessment theoretical frameworks and methodologies vary widely. Previous studies have shown that taxonomic...

Moëne, O. L., Larsson, M. 2023. A new tool for quantifying mouse facial expressions. ENeuro 10(2) ENEURO.0349-22.2022.

Facial expressions are an increasingly used tool to assess emotional experience and affective state during experimental procedures in animal models. Previous studies have successfully related specific facial features with different positive and negative valence situations...

Xu, J. J., Lucero, M. Y., Herndon, N. L. et al. 2023. Comparison of a minimally invasive transthoracic approach and a surgical method for intrapleural injection of tumor cells in mice. Comparative Medicine 73(2), 120–126.

Intrapleural injections can be used in mice to deliver therapeutic and diagnostic agents and to model human disease processes (for example, pleural fluid accumulation, malignant pleural disease, and lung cancers). In the context of establishing...

Dietrich, T., Aigner, A., Hildebrandt, A. et al. 2023. Nesting behavior is associated with body weight and grip strength loss in mice suffering from experimental arthritis. Scientific Reports 13(1), 23087.

Objective animal health evaluation is essential to determine welfare and discomfort in preclinical in vivo research. Body condition scores, body weight, and grimace scales are commonly used to evaluate well-being in murine rheumatoid arthritis (RA)...

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...

rueger, J. C., Boecker, M., Gauggel, S. et al. 2023. Using photographs for rating severity degrees of clinical appearance in research mice enables valid discrimination of extreme but not mild and moderate conditions: A pilot study. PLOS ONE 18(11), e0287965.

To ensure good animal welfare in laboratory research and in stockbreeding severity ratings of the animals´ wellbeing are essential. The current study investigated how valid raters can evaluate different severity degrees of clinical appearance and...

Littlewood, K. E., Heslop, M. V., Cobb, M. L. 2023. The agency domain and behavioral interactions: Assessing positive animal welfare using the Five Domains Model. Frontiers in Veterinary Science 10.
Martinez-Lopez, S., Angel-Gomis, E., Sanchez-Ardid, E. et al. 2023. The 3Rs in experimental liver disease. Animals 13(14), 2357.

Patients with cirrhosis present multiple physiological and immunological alterations that play a very important role in the development of clinically relevant secondary complications to the disease. Experimentation in animal models is essential to understand the...

Pérez-Martín, E., Coto-Vilcapoma, A., Castilla-Silgado, J. et al. 2023. Refining stereotaxic neurosurgery techniques and welfare assessment for long-term intracerebroventricular device implantation in rodents. Animals 13(16), 2627.

Stereotaxic surgeries enable precise access to specific brain regions, being of particular interest for chronic intracerebroventricular drug delivery. However, the challenge of long-term studies at this level is to allow the implantation of drug storage...

Reiber, M., Schumann, L. von, Buchecker, V. et al. 2023. Evidence-based comparative severity assessment in young and adult mice. PLOS ONE 18(10), e0285429.

In animal-based research, welfare assessments are essential for ethical and legal reasons. However, accurate assessment of suffering in laboratory animals is often complicated by the multidimensional character of distress and pain and the associated affective...

Rogers, L. J. 2023. Knowledge of lateralized brain function can contribute to animal welfare. Frontiers in Veterinary Science 10.

The specialized functions of each hemisphere of the vertebrate brain are summarized together with the current evidence of lateralized behavior in farm and companion animals, as shown by the eye or ear used to attend...

Štrbenc, M., Kuhar, U., Lainšček, D. et al. 2023. Rehoming and other refinements and replacement in procedures using golden hamsters in SARS-CoV-2 vaccine research. Animals 13(16), 2616.

Effective vaccines are needed to fight the COVID-19 pandemic. Forty golden hamsters were inoculated with two promising vaccine candidates and eighteen animals were used in pilot trials with viral challenge. ELISA assays were performed to...

Tanaka, Y., Nakata, T., Hibino, H. et al. 2023. Classification of multiple emotional states from facial expressions in head-fixed mice using a deep learning-based image analysis. PLOS ONE 18(7), e0288930.

Facial expressions are widely recognized as universal indicators of underlying internal states in most species of animals, thereby presenting as a non-invasive measure for assessing physical and mental conditions. Despite the advancement of artificial intelligence-assisted...

Martins, T., Matos, A. F., Soares, J. et al. 2022. Comparison of gelatin flavors for oral dosing of C57BL/6J and FVB/N mice. JAALAS 61(1), 89-95.

Precise oral dosing in rodents is usually achieved by intragastric gavage. If performed incorrectly due to technical difficulties, inexperience, or animal resistance, oral gavage may have animal welfare implications such as esophageal and gastric rupture...