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. 
Fitzwater, A., Zhang, L. 2024. A cost-effective restraint method for safer subcutaneous scruff injections and reducing stress in mice and handlers. Laboratory Animal Science Professional 12(1) (January/February), 52-53.

Subcutaneous injection is a vital technique in mouse-based biomedical research. Compared to other injections, the subcutaneous method poses fewer technical challenges and reduces acute toxicity risks due to slower absorption. Several suitable subcutaneous injection sites...

Silva-Almeida, C., Muniz, S. C. A., Jobim, C. M. N. et al. 2024. Perinatal environmental enrichment changes anxiety-like behaviours in mice and produces similar intergenerational benefits in offspring. Behavioural Brain Research 456, 114700.

Environmental enrichment implemented in early life is able to induce long-term changes in gene expression, synaptic function and behavioural responses. In this study, we evaluated the adult behavioural effects of perinatal environment enrichment in male...

Wang, Q., Wang, Y., Tian, Y. et al. 2024. Social environment enrichment alleviates anxiety-like behavior in mice: Involvement of the dopamine system. Behavioural Brain Research 456, 114687.

Rearing environment plays a vital role in maintaining physical and mental health of both animals and humans. Plenty of studies have proved that physical environment enrichment in adolescence has protective effects on emotion, social behavior...

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...

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...

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...

Jorge, S., Félix, L., Costas, B. et al. 2023. Housing conditions affect adult zebrafish (Danio rerio) behavior but not their physiological status. Animals 13(6), 1120.

Zebrafish is a valuable model for neuroscience research, but the housing conditions to which it is exposed daily may be impairing its welfare status. The use of environmental enrichment and the refinement of methodology for...

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...

Quante, S. M., Siewert, V., Palme, R. et al. 2023. The power of a touch: Regular touchscreen training but not its termination affects hormones and behavior in mice. Frontiers in Behavioral Neuroscience 17, 1112780.

Touchscreen-based procedures are increasingly used in experimental animal research. They not only represent a promising approach for translational research, but have also been highlighted as a powerful tool to reduce potential experimenter effects in animal...

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...

Vicentini, R. R., El Faro, L., Ujita, A. et al. 2023. Effects of training for first milking involving positive tactile stimulation on post-calving maternal behaviors in primiparous gyr dairy cows. Animals 13(5), 921.

In dairy systems with Zebu breeds, calves are not immediately separated from their dams after calving; consequently, maternal care and protective behavior are important, influencing both productive performance and stockpeople’s safety. Our objectives were to...

Watanabe, S. 2023. Are mirrors aversive or rewarding for mice? Insights from the mirror preference test. Frontiers in Behavioral Neuroscience 17, 1137206.

Research investigating the effects of mirror exposure in mice found that the presence of mirrors has similar effects to the presence of cage mates. Restraint in a small holder induces hyperthermia (stress-induce hyperthermia: SIH) in...

Watanabe, S. 2023. Infrared thermography for non-invasive measurement of social inequality aversion in rodents and potential usefulness for future animal-friendly studies. Frontiers in Behavioral Neuroscience 17, 1131427.

Infrared thermography is a method that detects thermal radiation energy and can measure the body surface temperature of animals from a distance. While rectal temperature has traditionally been used to measure animals’ core temperature, thermal...

Danforth, M. D., Clyde, V. L., Jourdan, B. et al. 2023. Blood pressure monitoring in zoologically managed bonobos (Pan paniscus). American Journal of Primatology 85(3), e23474.

In response to the growing evidence that hypertension may play a significant role in the development of cardiovascular disease (CVD) in bonobos, the Great Ape Heart Project established a finger blood pressure (BP) monitoring protocol...

Machado, M., Freitas Silveira, R. M., Machado Bittar, C. M. et al. 2023. Can the emotional state of calves be noticed by their facial expression and heart rate? Applied Animal Behaviour Science 260, 105874.

The aim of this study was to identify whether or not dairy calves change their facial expression and heart rate according to their emotional state when subjected to a stroking or umbrella stimulus. Thirty-two mixed-breed...

Alef, R., Blaser, R. E. 2023. Social group during housing and testing modulates the effect of ethanol on zebrafish (Danio rerio) behavior. Behavioural Processes 209, 104877.

Zebrafish (Danio rerio) are a popular model organism in behavioral pharmacology research due to many genetic and neurological similarities with humans. As a social species, the presence (or absence) of conspecifics during housing and testing...

Attokaren, M. K., Jeong, N., Blanpain, L. et al. 2023. BrainWAVE: A flexible method for noninvasive stimulation of brain rhythms across species. ENeuro 10(2) ENEURO.0257-22.2022.

Rhythmic neural activity, which coordinates brain regions and neurons to achieve multiple brain functions, is impaired in many diseases. Despite the therapeutic potential of driving brain rhythms, methods to noninvasively target deep brain regions are...

Fontana, B. D., Alnassar, N., Parker, M. O. 2023. Transgenerational effects of early-life stress on anxiety behavior in zebrafish (Danio rerio). Behavioural Processes 208, 104874.

Early-life adversity impacts on anxiety-related behaviors in adulthood. The effects of such adversity not only affect the animal itself, but can be passed on transgenerationally. Pervasive effects of experimentally-induced early-life stress (ELS) have been documented...

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...

Bakony, M., Kovács, L., Kézér, L. F. et al. 2023. The use of body surface temperatures in assessing thermal status of hutch-reared dairy calves in shaded and unshaded conditions. Frontiers in Veterinary Science 10.

The study was carried out in a Hungarian large-scale dairy farm during a 5-day period in hot August weather. Altogether 16 preweaning calves were chosen for the study. An agricultural mesh with 80% shielding was...

Bramati, G., Stauffer, P., Nigri, M. et al. 2023. Environmental enrichment improves hippocampus-dependent spatial learning in female C57BL/6 mice in novel IntelliCage sweet reward-based behavioral tests. Frontiers in Behavioral Neuroscience 17.

The IntelliCage is an automated home-cage system that allows researchers to investigate the spontaneous behavior and learning abilities of group-housed mice. The IntelliCage enables us to increase the standardization and reproducibility of behavioral outcomes by...

Brezov, D., Hristov, H., Dimov, D. et al. 2023. Predicting the rectal temperature of dairy cows using infrared thermography and multimodal machine learning. Applied Sciences 13(20), 11416.

The paper proposes an approach for estimating the rectal temperature of dairy cows based on the non-invasive real-time monitoring of their respiration rates and the temperature-humidity index (THI) of the environment, combined with the analysis...

Chiba, Y., Nozaki, I., Itoh, M. et al. 2023. Noninvasive measurement of blood calcium concentration using electrocardiography in peripartum Jersey cows. Frontiers in Veterinary Science 10.

We previously developed a noninvasive method for measuring blood calcium concentration (Ca) in Holstein cows on site using electrocardiographic (ECG) variables and calving number, based on a high positive correlation between Ca. Jersey cows easily...

Esparza, K. 2023, August. Moving away from soiled bedding sentinels—The (R)evolution in rodent health screening. Animal Technology and Welfare 22(2), 158–160.

Traditional health monitoring methods consisted of Soiled Bedding Sentinels (SBS (i.e. animals exposed to dirty bedding from colony animals)), which require the euthanasia of SBS. Numerous studies have demonstrated that SBS may not accurately represent...