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. 
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...

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)...

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...

Ludwig, J. L. 2020. Is that a rat in your pocket? A novel pocket method for rat restraint. Laboratory Animal Science Professional 8(1) (January/February), 48-49.

At the University of Illinois at Urbana- Champaign (UIUC), we routinely teach novice research personnel how to appropriately handle, restrain, and perform basic experimental techniques on rats. Barriers to teaching include fear of animal bites...

Zemanova, M. A. 2020. Towards more compassionate wildlife research through the 3Rs principles: Moving from invasive to noninvasive methods. Wildlife Biology 2020(1), no page numbers.

Research in ecology and wildlife biology remains crucial for increasing our knowledge and improving species management and conservation in the midst of the current biodiversity crisis. However, obtaining information on population status often involves invasive...

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...

Association of Primate Veterinarians. 2019. Association of Primate Veterinarians’ guidelines for nonhuman primate restraint. JAALAS 58(3), 282-284.

The Association of Primate Veterinarians (APV) recognizes that several forms of restraint, including physical and chemical, are necessary for the safe handling of nonhuman primates (NHPs). The following guidelines aim to provide information to researchers...

Makowska, I. J., Weary, D. M. 2019. A good life for laboratory rodents? ILAR Journal 60(3), 373-388.

Most would agree that animals in research should be spared “unnecessary” harm, pain, or distress, and there is also growing interest in providing animals with some form of environmental enrichment. But is this the standard...

Byrd, R., Boyd, S., Buckmaster, C. 2018. Rat thunder jacket— A zen experience. Laboratory Animal Science Professional 6(3) (September), 55-57.

Germ-free rats are fairly uncommon, relative to germ-free mice, and restraining these animals safely and effectively for compound administration and blood collection can be challenging. There are many commercially available varieties of restraint devices, but...

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...

Lipták, B., Kaprinay, B., Gáspárová, Z. 2017. A rat-friendly modification of the non-invasive tail-cuff to record blood pressure. Lab Animal 46(6), 251-253.

In animal models, blood pressure measurement methods can be either invasive (direct) or non-invasive (indirect). The non-invasive alternative involves applying a tail-cuff for blood pressure measurement. Current standardized restraint methods involve confining the laboratory animal...

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...

McMillan, J. L., Bloomsmith, M. A., Prescott, M. J. 2017. An international survey of approaches to chair restraint of nonhuman primates. Comparative Medicine 67(5), 442–451.

Specifically designed restraint chairs are the preferred method of restraint for research studies that require NHP to sit in place for sustained periods of time. In light of increasing emphasis on refinement of restraint to...

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...

Stuart, S., Robinson, E. S. J. 2015. Reducing the stress of drug administration: Implications for the 3Rs. Scientific Reports 5, 14288.

Restraint in animals is known to cause stress but is used during almost all scientific procedures in rodents, representing a major welfare and scientific issue. Administration of substances, a key part of most scientific procedures...

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...

Bode, A. E., Barber, H. 2014. Use of vinyl nonadhesive tape as an alternative for positioning rodents in small animal imaging. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 597-598. (Abstract #P185).

Specific positioning for different imaging modalities is essential in our small animal imaging core. While we have different animal holders designed to position the animal inside the MRI, additional securing of the animal to the...

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...

Pater, C. S. 2013. Rabbit hypnosis as a form of mild restraint: A forgotten method. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 615 (Abstract #PS42).

Rabbit hypnosis or “trancing” was a common restraint technique used for minor procedures such as: nail clipping, tooth trimming, eye exams, and subcutaneous injections. In years past the technique was originally used on pet rabbits...

Warwick, C., Arena, P., Lindley, S. et al. 2013. Assessing reptile welfare using behavioural criteria. In Practice 35(3), 123-131.

While clinical reptile medicine as a science is in its ascendancy among veterinary surgeons and other interested groups, familiarity with the often related issue of reptilian behavioural and psychological health appears less common. Behavioural change...