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. 
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...

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...

Ruvira, S., Rodríguez-Rodríguez, P., Cañas, S. et al. 2023. Evaluation of parameters which influence voluntary ingestion of supplements in rats. Animals 13(11), 1827.

Drug safety and efficacy studies frequently use oral gavage, but repetitive usage may cause problems. Administration through voluntary ingestion represents an opportunity for refinement. We aimed to develop a protocol for voluntary ingestion of gelatin-based...

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...

Alejandro, J., Yamanashi, Y., Nemoto, K. et al. 2023. Reducing stress and stereotypic behaviors in captive female pygmy slow lorises (Nycticebus pygmeaus). American Journal of Primatology 85(7), e23495.

Improving captive conditions of pygmy slow lorises (Nekaris and Nijman have recently suggested that the pygmy slow loris should be called the pygmy loris and is distinctive enough to warrant a new genus, Xanthonycticebu) (Nycticebus...

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...

Shanazz, K., Nalloor, R., Vazdarjanova, A. 2023. A mild stressor induces short-term anxiety and long-term phenotypic changes in trauma-related behavior in female rats. Frontiers in Behavioral Neuroscience 17.

IntroductionAnxiety and anxiety-influenced disorders are sexually dimorphic with women being disproportionately affected compared to men. Given the increased prevalence in women and the documented differences in anxiety and trauma behavior between male and female rats...

Goldsborough, Z., Sterck, E. H. M., de Waal, F. B. M. et al. 2022. Individual variation in chimpanzee (Pan troglodytes) repertoires of abnormal behaviour. Animal Welfare 31(1), 125-135.

Abnormal behaviour in captive animals is both pervasive and ambiguous. Although individual differences are central to the field of animal welfare, studies on abnormal behaviour predominantly employ quantitative, population-level approaches. For example, whereas previous studies...

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...

Habenicht, L. M., Staley, A. W., Clancy, B. M. et al. 2022. Characterization of a jumping stereotypy in gerbils (Meriones unguiculatus) and assessment of opaque tubing enrichment on stereotypies and breeding. JAALAS 61(2), 149-158.

Mongolian gerbils can develop stereotypic behaviors, including corner digging. At our institution, gerbils also engage in repetitive corner jumping, which we sought to characterize as a potentially novel stereotypy in gerbils. We then attempted to...

Buckmaster, C. L., Levesque, D., LaFollette, M. et al. 2022. Five hot topics in refinement of nonhuman primate neuroscience research. Laboratory Animal Science Professional 10(1) (January/February), 24-26.

Members of the North American 3Rs Collaborative (NA3RsC) refinement initiative have chosen to summarize developments in five hot topics of interest: 1. Tips for welfare-friendly transport, chairing, and restraint; 2. Guidance on refining food and...

Guerrero-Martin, S. M., Brill, S., Carlson, B. W. 2022. Development and implementation of a positive reinforcement training program for nonhuman primates in biomedical research. Laboratory Animal Science Professional 10(1) (January/February), 48-52.

Despite clear benefits of PRT for NHPs and biomedical research, investigators often view the investment in personnel expertise and time required to train animals as deterrents towards adopting PRT. We provide an example of how...

Hirata, S. 2022. Sky after 30 years: A brief biography of three biomedical research chimpanzees in Japan. Primates 63(2), 105–108.

This article describes the strategies employed by Kumamoto Sanctuary in Japan to integrate 3 retired chimpanzees – who each spent 30 years singly housed in a biomedical facility – with the sanctuary’s other residents.

Lutz, C. K., Coleman, K., Hopper, L.M. et al. 2022. Nonhuman primate abnormal behavior: Etiology, assessment, and treatment. American Journal of Primatology 84(6), e23380.

Across captive settings, nonhuman primates may develop an array of abnormal behaviors including stereotypic and self-injurious behavior. Abnormal behavior can indicate a state of poor welfare, since it is often associated with a suboptimal environment...

Bartlett, J., Davies, J., Purawijaya, D. et al. 2022. Refinement of handling and dosing methods for rats and mice. Animal Technology and Welfare 21(2), 120-124.

Modified Handling for Mice: Handling mice by gripping the base of the tail has been shown to negatively impact animal welfare by increasing anxiety and aversion to handling. We aimed to refi ne the dosing...

Donaldson-Wing, M. 2022. Medicated jelly as a replacement for injectables and the use of Maropitant to manage itchy skin in mice. Animal Technology and Welfare 21(2), 134-136.

It is desirable to administer drugs by the least invasive route to (1) optimise welfare, (2) reduce the risk of injury to animal handlers and (3) minimise the impact of restraint and transient pain on...

Franklin, A. N., Martin, A. L., Perlman, Siti Norsyuhada Kamaluddin et al. 2022. Functional analysis and successful treatment of a captive rhesus macaque’s disruptive behavior. Journal of Applied Animal Welfare Science 25(3), 287-296.

Functional analysis (FA) is a method developed and used by behavior analysts in human clinical settings to identify possible environmental variables that reinforce undesired behavior. FA is increasingly being applied to better understand the behavior...

Chesler, K. C., Motz, C. T., Bales, K. L. et al. 2022. Voluntary oral dosing for precise experimental compound delivery in adult rats. Laboratory Animals 56(2), 147-156.

Preclinical drug studies routinely administer experimental compounds to animal models with the goal of minimizing potential adverse events from the procedure. In this study, we assessed the ability to train adult male Long Evans rats...

Neto, T., Faustino-Rocha, A. I., Gil da Costa, R. M. et al. 2022. A quick and low-intensity method for oral administration to large numbers of mice: A possible alternative to oral gavage. Laboratory Animals 56(2), 185-190.

Oral administration of medication to experimental animals is a cause of significant stress. When coupled to animals who are already under strenuous circumstances due to the disease being modelled, there is a significant risk for...

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...

Fink, L. B., Mukobi, A., Gruber, L. et al. 2022. Longitudinal analysis of variability in fecal glucocorticoid metabolite concentrations in three orangutans (Pongo pygmaeus pygmaeus and Pongo pygmaeus abelii) before, during, and after transition from a regular habitat environment to temporary housing in indoor holding facilities. Animals 12(23), 3303.

Considerable research has been conducted on the effects of inter-institutional transfers, but far less consideration has been given to intra-institutional transfers and extended housing in off-habitat holding. On 15 May 2018, The Oregon Zoo’s orangutans...

Laméris, D. W., Verspeek, J., Salas, M. et al. 2022. Evaluating self-directed behaviours and their association with emotional arousal across two cognitive tasks in bonobos (Pan paniscus). Animals 12(21), 3002.

Self-directed behaviours (SDBs) are widely used as markers of emotional arousal in primates, and are commonly linked to negative arousal, or are used as indicators of stress or poor welfare. However, recent studies suggest that...

Müller, K., Lengheimer, T., Kral-Pointner, J. B. et al. 2022. Exposure to soiled bedding reduces abnormal repetitive behaviors in mice. Frontiers in Behavioral Neuroscience 16, 1062864.

Hygiene management protocols in laboratory mouse husbandries worldwide most commonly employ soiled bedding-exposed sentinel mice to monitor the occurrence of infections in mouse colonies. Using this approach, sentinel mice repeatedly receive a mixture of used...

Nuber, M., Gonzalez-Uarquin, F., Neufurth, M. et al. 2022. Development of a 3D simulator for training the mouse in utero electroporation. PLOS ONE 17(12), e0279004.

In utero electroporation (IUE) requires high-level training in microinjection through the mouse uterine wall into the lateral ventricle of the mouse brain. Training for IUE is currently being performed in live mice as no artificial...