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. 
Hickman, D., Fitz, S., Bernabe, C. et al. 2016. Evaluation of low versus high volume per minute displacement CO2 methods of euthanasia in the induction and duration of panic-associated behavior and physiology. Animals 6(8), 45.

Current recommendations for the use of CO 2 as a euthanasia agent for rats require the use of gradual fill protocols (such as 10% to 30% volume displacement per minute) in order to render the...

Lidster, K., Jefferys, J. G., Blümcke, I. et al. 2016. Opportunities for improving animal welfare in rodent models of epilepsy and seizures. Journal of Neuroscience Methods 260, 2-25.

Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs...

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...

Lidster, K., Jefferys, J. G., Blümcke, I. et al. 2016. Opportunities for improving animal welfare in rodent models of epilepsy and seizures. Journal of Neuroscience Methods 260, 2-25.

Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs...

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...

Cloutier, S., Wahl, K. L., Panksepp, J. et al. 2015. Playful handling of laboratory rats is more beneficial when applied before than after routine injections. Applied Animal Behaviour Science 164, 81-90.

The ability of positive affective states to counteract negative states engendered by routine medical procedures remains poorly studied. In laboratory rats, positive affect typically associated with rough-and-tumble play can be induced through human “hand play”...

Bayne, K. A., Beaver, B. V., Mench, J. A. et al. 2015. Laboratory animal behavior. In: Laboratory Animal Medicine, 3rd edition. Fox, J. G., Anderson, L., Otto, G., et al. (eds). Elsevier, Inc., Amsterdam, NL. pp. 1617-1651.

The study of laboratory animal behavior has increased steadily over the last decade, with expanding emphasis on a variety of commonly used species. In the United States, this trend was initially focused on species for...

Hawkins, P., Armstrong, R., Boden, T. et al. 2015. Applying refinement to the use of mice and rats in rheumatoid arthritis research. Inflammopharmacology 23, 131–150.

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments...

Nicholson, G., Sheldon, E. L., Hamilton, J. et al. 2014. Sand pools as a novel enrichment for rabbits. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 571. (Abstract #P83).

For anyone who has housed rabbits in an artificial plastic environment, what to provide as a nonfood enrichment can be an issue. Nonfood enrichment, or environmental enrichment, can be any toy, engaging sights or sounds...

Hori, M., Yamada, K., Ohnishi, J. et al. 2014. Tickling during adolescence alters fear-related and cognitive behaviors in rats after prolonged isolation. Physiology & Behavior 131, 62-67.

Social interactions during adolescence are important especially for neuronal development and behavior. We recently showed that positive emotions induced by repeated tickling could modulate fear-related behaviors and sympatho-adrenal stress responses. In the present study, we...

Hawkins, P. 2014. Refining housing, husbandry and care for animals used in studies involving biotelemetry. Animals 4(2), 361-373.

Biotelemetry can contribute towards reducing animal numbers and suffering in disciplines including physiology, pharmacology and behavioural research. However, the technique can also cause harm to animals, making biotelemetry a ‘refinement that needs refining’. Current welfare...

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...

Cloutier, S., Baker, C., Wahl, K. et al. 2013. Playful handling as social enrichment for individually- and group-housed laboratory rats. Applied Animal Behaviour Science 143(2-4), 85-95.

Social housing is recommended for laboratory rats because they are highly social mammals but research constraints or medical issues often demand individual housing and, when social housing is practiced, it typically involves housing with only...

Wong, D., Makowska, I. J., Weary, D. M. 2013. Rat aversion to isoflurane versus carbon dioxide. Biology Letters 9(1), 20121000.

Some experts suggest that sedation of laboratory rodents with isoflurane before euthanasia with carbon dioxide (CO2) is a humane alternative to euthanasia with CO2 alone, but little research has compared aversion with these agents. Albino...

Chisholm, J., De Rantere D., Fernandez, N. J. et al. 2013. Carbon dioxide, but not isoflurane, elicits ultrasonic vocalizations in female rats. Laboratory Animals 47(4), 324-7.

Gradual filling of a chamber with carbon dioxide is currently listed by the Canadian Council on Animal Care guidelines as a conditionally acceptable method of euthanasia for rats. Behavioural evidence suggests, however, that exposure to...

Wolfensohn, S., Hawkins, P., Lilley, E. et al. 2013. Reducing suffering in experimental autoimmune encephalomyelitis (EAE). Journal of Pharmacological and Toxicological Methods 67(3), 169-176.

This report is based on discussions and submissions from an expert working group consisting of veterinarians, animal care staff and scientists with expert knowledge relevant to the field. It aims to facilitate the implementation of...

Wolfensohn, S., Hawkins, P., Lilley, E. et al. 2013. Reducing suffering in animal models and procedures involving seizures, convulsions and epilepsy. Journal of Pharmacological and Toxicological Methods 67(1), 9-15.

This report is based on discussions and submissions from an expert working group consisting of veterinarians, animal care staff and scientists with expert knowledge relevant to the field and aims to facilitate the implementation of...

Hosey, G., Melfi, V. 2012. Human-animal bonds between zoo professionals and the animals in their care. Zoo Biology 31(1), 13-26.

Some human-animal relationships can be so positive that they confer emotional well-being to both partners and can thus be viewed as bonds. In this study, 130 delegates at zoo research and training events completed questionnaires...

Costa, R., Tamascia, M. L., Nogueira, M. D. et al. 2012. Handling of adolescent rats improves learning and memory and decreases anxiety. JAALAS 51(5), 548-553.

Some environmental interventions can result in physiologic and behavioral changes in laboratory animals. In this context, the handling of adolescent or adult rodents has been reported to influence exploratory behavior and emotionality. Here we examined...

Cloutier, S., Panksepp, J., Newberry, R. C. 2012. Playful handling by caretakers reduces fear of humans in the laboratory rat. Applied Animal Behaviour Science 140(3-4), 161-171.

Handling of laboratory rats can increase physiological and emotional stress, leading to a fearful relationship with humans. We hypothesized that the affective quality of handling techniques used during routine care influences the animals' fear of...

Swennes, A. G., Alworth, L. C., Harvey, S. B. et al. 2011. Human handling promotes compliant behavior in adult laboratory rabbits. JAALAS 50(2), 41-45.

Routine laboratory procedures can be stressful for laboratory animals. We wanted to determine whether human handling of adult rabbits could induce a degree of habituation, reducing stress and facilitating research-related manipulation. To this end, adult...

Claxton, A. M. 2011. The potential of the human-animal relationship as an environmental enrichment for the welfare of zoo-housed animals. Applied Animal Behaviour Science 133(1), 1-10.

Environmental enrichment strategies are used to improve both the physiological and psychological welfare of captive animals, which can be achieved by increasing the expression of natural behaviour and decreasing abnormal behaviours. Examples of successful environmental...

Stewart, K. 2010. Effects of increased interaction between research rodents and their handlers. Animal Welfare Institute (AWI) Quarterly 59(1) Winter, 28-29.

We conclude that handling experimental animals more often than only at the time their cage is changes is beneficial.

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...