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...

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...

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...

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)...

Giral, M., Armengol, C., Gavaldà, A. 2022. Physiologic effects of housing rats in metabolic cages. Comparative Medicine 72(5), 298–305.

Currently, metabolic cages (MC) are the only way to achieve serial sampling of urine and feces in rodents. However, the use of this caging creates a dramatic change from an animal’s usual microenvironment. Here we...

Sørensen, D., Cloutier, S., Gaskill, B. (Eds.). 2021. Animal-centric Care and Management - Enhancing Refinement in Biomedical Research. CRC Press, Boca Raton, FL.

The concept of the 3Rs (Refinement, Reduction and Replacement) has been used as a framework for improving the welfare of laboratory animals for the last half century. By establishing an animal-centric view on housing and...

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...

Prior, H., Blunt, H., Crossman, L. et al. 2021. Refining procedures within regulatory toxicology studies: Improving animal welfare and data. Animals 11(11), 3057.

During the development of potential new medicines or agrochemicals, an assessment of the safety profile to humans and environmental species is conducted using a range of different in silico and in vitro techniques in conjunction...

Locklear, J., Whiteside, T. E. 2021. Optimal colloidal water gel type and novel placement for frequent travelers. Laboratory Animal Science Professional 9(6) (November/December), 38-40.

During transportation, animals must have a water source available to prevent dehydration. Some shipping facilities use potatoes whereas, others use colloidal water gels that provide a uniform water source. The problem occurs when colloidal water...

Ballantine, A., Rodgers, D., Watts, C. et al. 2020. The cotton rat – a new challenge. Animal Technology and Welfare 19(1), 92-95.

This poster describes how the Animal Technologists at Envigo adapted their current practices and procedures for a new species at their laboratory: the cotton rat. The paper describes cotton rat biology and behaviour; housing; environmental...

Reinhardt, V. (ed.) 2020. It’s Okay to Cry - Discussions by the Laboratory Animal Refinement & Enrichment Forum [LAREF], Volume V. Animal Welfare Institute, Washington, DC.

This is the 5th volume of selected discussions that took place on the electronic Laboratory Animal Refinement & Enrichment Forum between February 2016 and December 2019. The forum was created in October 2002; it allows...

Munari, C., Ponzio, P., Macchi, E. et al. 2020. A multifactorial evaluation of different reproductive rhythms and housing systems for improving welfare in rabbit does. Applied Animal Behaviour Science 230, 105047.

The most widespread reproductive rhythm practiced in rabbit farming is based on artificial insemination (AI) performed at around 11 days pospartum. This approach results in high production rates, but requires high yearly replacement of animals...

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...

Animal Welfare Institute. 2019. A new beginning for retired laboratory rabbits. Animal Welfare Institute (AWI) Quarterly 68(4) Winter, 10-11.

This article describes the rehoming of 10 laboratory female rabbits now living as a group in a private shelter.

McMillan, F. D. (ed). 2019. Mental Health and Well-being in Animals (2nd ed). CABI, Wallingford, UK.

This second edition is fully revised, expanded, and comprehensively updated with the most current knowledge about the full array of mental health issues seen in animals. Written by key opinion leaders, internationally-recognized experts and specialists...

Peric, T., Comin, A., Corazzin, M., et al. 2018. Hair cortisol concentrations in New Zealand white rabbits subjected to surgery. Animal Welfare 27(1), 13-20.

The aim of this study was to assess hair cortisol concentrations in New Zealand white rabbits (Oryctolagus cuniculus) that were subjected to relocation and surgery to evaluate HPA-axis activity; in addition, we used this marker...

Harikrishnan, V. S., Hansen, A. K., Abelson, K. S. P. et al. 2018. A comparison of various methods of blood sampling in mice and rats: Effects on animal welfare. Laboratory Animals 52(3), 253-264.

This study was conducted to investigate the effects of blood sampling on animal welfare in a total of 60 NTac:SD rats and 72 C57BL/6NTac mice of both sexes. Blood was sampled either by sublingual vein...

Hoffman, J. F., Fan, A. X., Neuendorf, E. H. et al. 2018. Hydrophobic sand versus metabolic cages: A comparison of urine collection methods for rats (Rattus norvegicus). JAALAS 57(1), 51-57.

A common method for urine collection from rats requires the use of a metabolic cage, thus exposing animals to extended periods of isolation in an unfamiliar cage with a wire-mesh floor. A new method involving...

Wang, R., Hausknechta, K. A., Haj-Dahmane, S. et al. 2018. Decreased environmental complexity during development impairs habituation of reinforcer effectiveness of sensory stimuli. Behavioural Brain Research 337, 53-60.

Previous research has shown that rats reared in simple/impoverished environments demonstrate greater repetitive responding for sensory reinforcers (e.g., light onset). Moreover, the brains of these rats are abnormally developed, compared to brains of rats reared...

Taylor, R. M., Miller, P. R., Ebrahimi, P. et al. 2018. Minimally-invasive, microneedle-array extraction of interstitial fluid for comprehensive biomedical applications: Transcriptomics, proteomics, metabolomics, exosome research, and biomarker identification. Laboratory Animals 52(5), 526–530.

Interstitial fluid (ISF) has recently garnered interest as a biological fluid that could be used as an alternate to blood for biomedical applications, diagnosis, and therapy. ISF extraction techniques are promising because they are less...

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...

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...

Rodrigues, M. V., de Castro, S. O., de Albuquerque, C. Z. 2017. The gingival vein as a minimally traumatic site for multiple blood sampling in guinea pigs and hamsters. PLOS ONE 12(5), e0177967.

Laboratory animals are still necessary in scientific investigation and vaccine testing, but while novel methodological approaches are not available for their replacement, the search for new, humane, easy, and painless methods is necessary to diminish...

Amen, E. M., Brecheisen, M., Sach-Peltason, L. et al. 2017. Refinement of a model of repeated cerebrospinal fluid collection in conscious rats. Laboratory Animals 51(1), 44-53.

The cannulation of the cisterna magna in rats for in vivo sampling of cerebrospinal fluid serves as a valuable model for studying the delivery of new drugs into the central nervous system or disease models...