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. 
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...

Lupfer, G., Brandenburger, A., Machado, M. et al. 2023. Ultrasonic vocalizations near 30 kHz may indicate excitement rather than distress in female Wistar rats. Applied Animal Behaviour Science 261, 105881.

Rats emit ultrasonic vocalizations (USVs), sometimes referred to as 50-kHz vocalizations, during activities such as play and lower-frequency USVs, sometimes referred to as 22-kHz vocalizations, when experiencing distress. Definitions of 22-kHz vocalizations vary in terms...

Broadfoot, C. K., Lenell, C., Kelm-Nelson, C. A. et al. 2023. Effects of social isolation on 50-kHz ultrasonic vocalizations, affective state, cognition, and neurotransmitter concentrations in the ventral tegmental and locus coeruleus of adult rats. Behavioural Brain Research 437, 114157.

Vocal communication, cognition, and affective state are key features of sustained health and wellness, and because vocalizations are often socially-motivated, social experience likely plays a role in these behaviors. The monoaminergic systems of the ventral...

Van Loo, P. L. P., Janssens, M. R. E. 2023. Why all healthy laboratory animals should be rehomed, no matter how small. Animals 13(17), 2727.

This paper explores the ethical imperative of rehoming all healthy animals of sentient species after experiments have finished or when they have become otherwise redundant. We take into account disparate perspectives in animal ethics and...

Tivey, E. K. L., Martin, J. E., Brown, S. M. et al. 2022. Sex differences in 50 kHz call subtypes emitted during tickling-induced playful behaviour in rats. Scientific Reports 12(1), 15323.

‘Tickling’ induces positive affective states in laboratory rats as evidenced by the production of 50-kHz ultrasonic vocalisations (USVs), although this has mostly been investigated in males. Juvenile rats emit distinctive 50-kHz USV subtypes. Frequency-modulated (FM)...

Carbone, L. 2021. Estimating mouse and rat use in American laboratories by extrapolation from Animal Welfare Act-regulated species. Scientific Reports 11(1), 493.

Alone among Western nations, the United States has a two-tier system for welfare protections for vertebrate animals in research. Because its Animal Welfare Act (AWA) excludes laboratory rats and mice (RM), government veterinarians do not...

Seidisarouei, M., van Gurp, S., Pranic, N. M. et al. 2021. Distinct profiles of 50 kHz vocalizations differentiate between social versus non-social reward approach and consumption. Frontiers in Behavioral Neuroscience 15, 693698.

Social animals tend to possess an elaborate vocal communication repertoire, and rats are no exception. Rats utilize ultrasonic vocalizations (USVs) to communicate information about a wide range of socially relevant cues, as well as information...

Brudzynski, S. M. 2019. Emission of 22 kHz vocalizations in rats as an evolutionary equivalent of human crying: Relationship to depression. Behavioural Brain Research 363, 1-12.

There is no clear relationship between crying and depression based on human neuropsychiatric observations. This situation originates from lack of suitable animal models of human crying. In the present article, an attempt will be made...

Colby, L. A., Nowland, M. H., Kennedy, L. H. 2019. Clinical Laboratory Animal Medicine: An Introduction (5th ed). Wiley-Blackwell, Ames, IA.

The revised fifth edition of Clinical Laboratory Animal Medicine: An Introduction is an accessible guide to basic information for conducting animal research safely and responsibly. It includes a review of the unique anatomic and physiologic...

Barker, T. H., George, R. P., Howarth, G. S. et al. 2017. Assessment of housing density, space allocation and social hierarchy of laboratory rats on behavioural measures of welfare. PLOS ONE 12(9), e0185135.

Minimum space allowances for laboratory rats are legislated based on weight and stocking rates, with the understanding that increased housing density encourages crowding stress. However, there is little evidence for these recommendations, especially when considering...

Burke, C. J., Kisko, T. M., Swiftwolfe, H. et al. 2017. Specific 50-kHz vocalizations are tightly linked to particular types of behavior in juvenile rats anticipating play. PLOS ONE 12(5), e0175841.

Rat ultrasonic vocalizations have been suggested to be either a byproduct of physical movement or, in the case of 50-kHz calls, a means to communicate positive affect. Yet there are up to 14 distinct types...

Pinelli, C., Leri, F., Turner, P. 2017. Long term physiologic and behavioural effects of housing density and environmental resource provision for adult male and female Sprague Dawley rats. Animals 7(6), 44.

There is considerable interest in refining laboratory rodent environments to promote animal well-being, as well as research reproducibility. Few studies have evaluated the long term impact of enhancing rodent environments with resources and additional cagemates...

Jones, T., Robinson, M., Leach, M. et al. 2017. Ultrasonic vocalisation as a measure of positive welfare in rats. Animal Technology and Welfare 16(2), 127-129.

Studies of animal welfare in laboratory animals have historically relied on the measurement of negative indicators rather than the assessment of positive indicators of welfare. Practical methods of welfare assessment are required to allow refinement...

National Health and Medical Research Council [NHMRC]. 2016. Principles and guidelines for the care and use of non-human primates for scientific purposes. National Health and Medical Research Council: Canberra, Australia, 25 pp.

The Principles and guidelines for the care and use of non-human primates for scientific purposes is a revision of NHMRC’s Policy on the care and use of non-human primates for scientific purposes 2003 (the Policy)...

Kisko, T. M., Himmler, B. T., Himmler, S. M. et al. 2015. Are 50-kHz calls used as play signals in the playful interactions of rats? II. Evidence from the effects of devocalization. Behavoural Processes 111, 25-33.

During playful interactions, juvenile rats emit many 50-kHz ultrasonic vocalizations, which are associated with a positive affective state. In addition, these calls may also serve a communicative role – as play signals that promote playful...

Kisko, T. M., Euston, D. R., Pellis, S. M. 2015. Are 50-khz calls used as play signals in the playful interactions of rats? III. The effects of devocalization on play with unfamiliar partners as juveniles and as adults. Behavioural Processes 113, 113-121.

When playing, rats emit 50-kHz calls which may function as play signals. A previous study using devocalized rats provides support for the hypothesis that 50-kHz function to promote and maintain playful interactions (Kisko et al...

Pearson, B. L., Reeder, D. M., Judge, P. G. 2015. Crowding increases salivary cortisol but not self-directed behavior in captive baboons. American Journal of Primatology 77, 462-67.

Reduced space can lead to crowding in social animals. Crowding increases the risk of agonistic interactions that, in turn, may require additional physiological defensive coping mechanisms affecting health. To determine the stress induced from increased...

Himmler, B.T., Kisko, T.M., Euston, D.R. et al. 2014. Are 50-kHz calls used as play signals in the playful interaction of rats? I. Evidence from the timing and context of their use. Behavioural Processes 106, 60-66.

During playful interactions, rats emit increased levels of 50-kHz vocalizations. It is possible that these vocalizations are used as play signals that promote and maintain playful contact. The study investigated this possibility. It was predicted...

Yuki, S., Okanoya, K. 2014. Behavioral correlates of 50-kHz ultrasonic vocalizations in rats: Progressive operant discrimination learning reduces frequency modulation and increases overall amplitude. Animal Behavior and Cognition 1(4), 452–463.

Ultrasonic vocalizations (USVs) in rats are thought to contain ecological signals reflecting emotional states. These USVs are centered on 50-kHz, and frequency modulation (FM) is hypothesized to indicate positive emotion; however, results from recent studies...

Hrapkiewicz, K., Colby, L. A., Denison, P. 2013. Clinical Laboratory Animal Medicine: An Introduction (4th Ed). Wiley-Blackwell, Ames, IA.

Clinical Laboratory Animal Medicine: An Introduction, Fourth Edition offers a user-friendly guide to the unique anatomy and physiology, care, common diseases, and treatment of small mammals and nonhuman primates. Carefully designed for ease of use...

Howard, B., Nevalainen, T., Perretta, G. (ed). 2010. The COST Manual of Laboratory Animal Care and Use: Refinement, Reduction, and Research (1st Ed). CRC Press, Boca Raton, FL.

COST Action B-24 established four working groups to research and discuss issues relevant to laboratory animal science. These included the housing of animals, environmental needs, refinement of procedures, genetically modified animals, and cost-benefit analysis. Based...

Bayne, K. 2010. Enrichment and behavioral management programs around the world. Enrichment Record 4, 4-7.

To do justice to the diverse approaches to enrichment and behavioral management around the world would entail a discussion beyond the limits of this publication. Therefore, guidelines and regulations in a representative sample of countries...

Taylor K. 2010. Reporting the implementation of the three Rs in European primate and mouse research papers: Are we making progress? Alternatives to Laboratory Animals 38(6), 495-517.

It is now more than 20 years since both Council of Europe Convention ETS123 and EU Directive 86/609/EEC were introduced, to promote the implementation of the Three Rs in animal experimentation and to provide guidance...

Onbasilar, E. E., Onbasilar, Í. 2007. Effect of cage density and sex on growth, food utilization and some stress parameters of young rabbits. Scandinavian Journal of Laboratory Animal Science 34(3),189-195.

The aim of the experiment was to study the effects of cage density (1, 3 and 5 rabbits per cage) and sex (male and female) on stress parameters of young rabbits. A total of 90...

Conour, L. A., Murray, K. A., Brown, M. J. 2006. Preparation of animals for research -- Issues to consider for rodents and rabbits. ILAR Journal 47(4), 283-293.

This article provides details to consider when preparing to use animals in biomedical research. The stress of transport and receipt of animals into a new environment mandate the need for a period of stabilization and...