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. 
Sauer, M., Fleischmann, T., Lipiski, M. et al. 2016. Buprenorphine via drinking water and combined oral-injection protocols for pain relief in mice. Applied Animal Behaviour Science 185, 103-112.

Buprenorphine is the opioid analgesic most commonly used in laboratory mice. However, to maintain therapeutically effective serum levels, repeated injections are required. To overcome negative aspects of restraint and injection, oral self-administration is a promising...

Zatroch, K. K., Knight, C. G., Reime, J. N. et al. 2017. Refinement of intraperitoneal injection of sodium pentobarbital for euthanasia in laboratory rats (Rattus norvegicus). BMC Veterinary Research 13, 60.

Background: The Canadian Council on Animal Care and American Veterinary Medical Association classify intraperitoneal (IP) pentobarbital as an acceptable euthanasia method in rats. However, national guidelines do not exist for a recommended dose or volume...

Herndon, N. L., Bandyopadhyay, S., Hod, E. A. et al. 2016. Sustained-release buprenorphine improves postsurgical clinical condition but does not alter survival or cytokine levels in a murine model of polymicrobial sepsis. Comparative Medicine 66(6), 455–462.

Cecal ligation and perforation (CLP) is a common technique for studying sepsis in mice. Because of the invasiveness of the procedure and its effects on clinical condition, many animal care and use committees require the...

McEntee, D., Borg, K., Markiewicz, V. 2016. Establishment of a home-cage in vivo method of New Zealand white rabbit urine collection. Laboratory Animal Science Professional 4(4) (December), 44-46.

The most common methods for rabbit urine collection are newborn stroking, cystocentesis, and transfer to a metabolism cage.2 None of these options allow for a significant, quality amount of urine to be collected in vivo...

Tokumaru, R. S., Ades, C., Monticelli, P. F. 2015. Social support does not require attachment: Any conspecific tranquilizes isolated guinea-pig pups. Applied Animal Behaviour Science 171, 197-203.

Guinea pig pups produce typical distress whistles when isolated. Whistles’ frequency is decreased or abolished when they contact with the mother and, to a lesser degree, a sibling or even an unfamiliar female, is regained...

Miller, A., Kitson, G., Skalkoyannis, B. et al. 2015. The effect of isoflurane anaesthesia and buprenorphine on the mouse grimace scale and behaviour in CBA and DBA/2 mice. Applied Animal Behaviour Science 172, 58-62.

Prevention or alleviation of pain in laboratory mice is a fundamental requirement of in vivoresearch. The mouse grimace scale (MGS) has the potential to be an effective and rapid means of assessing pain and analgesic...

Wickremsinhe, E. R., Perkins, E. J. 2015. Using dried blood spot sampling to improve data quality and reduce animal use in mouse pharmacokinetic studies. JAALAS. 54(2), 139-144.

Traditional pharmacokinetic analysis in nonclinical studies is based on the concentration of a test compound in plasma and requires approximately 100 to 200 μL blood collected per time point. However, the total blood volume of...

Caron, A., Lelong, C., Pascual, M. H. et al. 2015. Miniaturized blood sampling techniques to benefit reduction in mice and refinement in nonhuman primates: Application to bioanalysis in toxicity studies with antibody-drug conjugates. JAALAS 54(2), 145-152.

Minimizing the number of animals in regulatory toxicity studies while achieving study objectives to support the development of future medicines contributes to good scientific and ethical practices. Recent advances in technology have enabled the development...

Miller, A. L., Leach, M. C. 2015. Using the mouse grimace scale to assess pain associated with routine ear notching and the effect of analgesia in laboratory mice. Laboratory Animals 49(2), 117-120.

Social housing is recommended where possible for laboratory mice. In order to achieve this, mice must be individually identifiable. Although, various methods are available, permanent identification is often required, such as ear notching. This method...

Moody, C. M., Makowska, I. J., Weary, D. M. 2015. Testing three measures of mouse insensibility following induction with isoflurane or carbon dioxide gas for a more humane euthanasia. Applied Animal Behaviour Science 163, 183-87.

Laboratory mice are commonly killed via exposure to gradually increasing concentrations of isoflurane and carbon dioxide (CO2) gas. Once rendered insensible using isoflurane or CO2, a high concentration of CO2 is used to decrease time...

Boulanger Bertolus, J., Nemeth, G., Makowska, I. J. et al. 2015. Rat aversion to sevoflurane and isoflurane. Applied Animal Behaviour Science 164, 73-80.

Virtually all rodents used in research are eventually euthanized. Best practice is to anaesthetize these animals before euthanasia using a halogenated anaesthetic such as isoflurane. Exposure to isoflurane is aversive, but less so than exposure...

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...

Cesarovic, N., Arras, M., Jirkof, P. 2014. Impact of inhalation anaesthesia, surgery and analgesic treatment on home cage behaviour in laboratory mice. Applied Animal Behaviour Science. 157, 137-145.

Anaesthesia and analgesia are used frequently in laboratory routine to ensure animal welfare and good scientific outcomes in experiments that may elicit pain or require immobilisation of the animal. However, there is concern regarding the...

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...

Allaire. A. C., Boule, S. 2014. Refining blood collection techniques to improve animal welfare and sample quality. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 605-606. (Abstract #P212).

An effort to refine rodent blood collection techniques resulted in an examination of alternative methodologies to improve animal welfare and sample quality. Disease model or repeated sample collection resulted in inadequate sample volume, occasional hemolysis...

Bratcher, N. A., Ebert, P. A., Buck, W. et al. 2014. Refinement and efficiency through serial microsampling: Cost:benefit analysis. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 580. (Abstract #P121).

Advances in bioanalytic methods allow for accurate plasma drug level measurement in small sample volumes. Decreased sample volumes enable serial blood sample collection from one rodent, rather than terminal or sparse sampling from multiple rodents...

Tupper, T., Manning, H., Turner, D. et al. 2014. An innovative restraint device for the placement of intravenous tail vein catheters in anesthetized mice. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 584. (Abstract #P136).

Consistently accurate intravenous tail vein administration of radiopharmaceuticals in anesthetized mice is a critical component of successful PET/CT imaging in the preclinical setting. Injectable anesthetics are often not suitable for PET imaging and commercially available...

Torres, M. 2014. Refining methods for mouse hepatic biopsy. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 557-558 (Abstract #P32).

The mouse is a commonly used species in liver research such as oncology, toxicology, and disease models. The ability to collect specimens of liver is vital to such research. Such studies require either a major...

Teilmann, A. C., Madsen, A. N., Holst, B. et al. 2014. Impact of blood sampling procedures on the welfare of laboratory mice. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 600-601. (Abstract #P195).

A previous study showed that blood sampling either automatically, through a catheter, or by puncture of the tail vein is less stressful than facial vein phlebotomy in mice. We decided to investigate how facial vein...

Cloutier, S., Wahl, K., Baker, C. et al. 2014. The social buffering effect of playful handling on responses to repeated intraperitoneal injections in laboratory rats. JAALAS 53(2), 168-173.

Handling small animals for veterinary and experimental procedures can negatively affect animal wellbeing. We hypothesized that playful handling (tickling) would decrease stress associated with repeated injections in adult laboratory rats, especially those with prior tickling...

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...

Lambeth, S. P., Schapiro, S. J., Bernacky, B. J. et al. 2013. Establishing 'quality of life' parameters using behavioural guidelines for humane euthanasia of captive non-human primates. Animal Welfare 22(4) 429-435.

Chronic pain and distress are universally accepted conditions that may adversely affect an animal’s quality of life (QOL) and lead to the humane euthanasia of an animal. At most research institutions and zoological parks in...

Voigt, C. C., Klockner, P., Touma, C. et al. 2013. Hormonal stress response of laboratory mice to conventional and minimally invasive bleeding techniques. Animal Welfare 22(4), 449-455.

Conventional bleeding of small laboratory animals is often associated with stress and injuries that can cause haematomas, inflammation and ultimately the death of animals under investigation. Here, we used faecal glucocorticoid metabolites as an indicator...

Sadler, A. M., Bailey, S. J. 2013. Validation of a refined technique for taking repeated blood samples from juvenile and adult mice. Laboratory Animals 47(4), 316-319.

Repeated blood sampling from laboratory animals is desirable in certain experimental designs and also for reducing the number of animals used in research. Biochemical methods for analysing blood samples require only small blood volumes to...