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. 
Guedes, S. R., Valentim, A. M., Antunes, L. M. 2017. Mice aversion to sevoflurane, isoflurane and carbon dioxide using an approach-avoidance task. Applied Animal Behaviour Science 189, 91-97.

Euthanasia of laboratory animals is one of the main concerns for animal welfare, especially the use of carbon dioxide (CO2) which has been described to induce aversive-like behaviours. In order to refine mass euthanasia in...

Makowska, I. J., Weary, D. M. 2016. Differences in anticipatory behaviour between rats (Rattus norvegicus) housed in standard versus semi-naturalistic laboratory environments. PLOS ONE 11(1), e0147595.

Laboratory rats are usually kept in relatively small cages, but research has shown that they prefer larger and more complex environments. The physiological, neurological and health effects of standard laboratory housing are well established, but...

Valentim, A. M., Guedes, S. R., Pereira, A. M. et al. 2016. Euthanasia using gaseous agents in laboratory rodents. Laboratory Animals 50(4), 241-253.

Several questions have been raised in recent years about the euthanasia of laboratory rodents. Euthanasia using inhaled agents is considered to be a suitable aesthetic method for use with a large number of animals simultaneously...

Powell, K., Ethun, K., Taylor, D. K. 2016. The effect of light level, CO2 flow rate, and anesthesia on the stress response of mice during CO2 euthanasia. Lab Animal 45(10), 386-395.

Euthanasia protocols are designed to mitigate the stress experienced by animals, and an environment that induces minimal stress helps achieve that goal. A protocol that is efficient and practical in a typical animal research facility...

Hawkins, P., Prescott, M., Carbone, L. et al. 2016. A good death? Report of the second Newcastle meeting on laboratory animal euthanasia. Animals 6(9), 50.

Millions of laboratory animals are killed each year worldwide. There is an ethical, and in many countries also a legal, imperative to ensure those deaths cause minimal suffering. However, there is a lack of consensus...

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...

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...

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...

Heyse, N. C., Brenes, J. C., Schwarting, R. K. W. 2015. Exercise reward induces appetitive 50-kHz calls in rats. Physiology & Behavior 147, 131-140.

Rats express affective states by visible behaviors (like approach or flight) and through different kinds of ultrasonic vocalizations (USV). 50-kHz calls are thought to reflect positive affective states since they occur during rewarding situations like...

Bartal, I. B.-A., Rodgers, D. A., Sarria, M. S. et al. 2014. Pro-social behavior in rats is modulated by social experience. eLife 3, e01385.

In mammals, helping is preferentially provided to members of one’s own group. Yet, it remains unclear how social experience shapes pro-social motivation. We found that rats helped trapped strangers by releasing them from a restrainer...

Jones, C. E., Riha, P. D., Gore, A. C. et al. 2014. Social transmission of Pavlovian fear: Fear-conditioning by-proxy in related female rats. Animal Cognition 17(3), 827–834.

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a foot-shock) leads to associative learning such that the tone alone will elicit a conditioned response (e.g., freezing)...

Makowska, I. J., Weary, D. M. 2013. Assessing the emotions of laboratory rats. Applied Animal Behaviour Science 148, 1-12.

Rats are one of the most commonly used species in research, and decades of testing have yielded a large amount of information pertaining to their experience of emotion. The aim of this review is to...

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...

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...

Coleman, K. 2012. Individual differences in temperament and behavioral management practices for nonhuman primates. Applied Animal Behaviour Science 137(3-4), 106-113.

This review will examine how individual differences in temperament might affect, or be affected by, behavioral management practices for captive primates. Measuring temperament may help us predict the outcome of social introductions. It can also...

Gewin, V. 2011. Rats free each other from cages. Nature News.

Following a two-week introduction period, pairs of rats were put inside an arena. One was trapped inside a central restrainer, while the other roamed free in the larger space. By day six or seven, on...

Brydges, N. M., Leach, M., Nicol, K. et al. 2011. Environmental enrichment induces optimistic cognitive bias in rats. Animal Behaviour 81(1), 169-175.

People's affective or emotional state can alter their cognitive processing, biasing interpretation of ambiguous stimuli. Those in a more positive state interpret such stimuli in a more optimistic manner than those in a negative state...

Õkva, K., Nevalainen, T., Mauranen, K. et al. 2010. The effect of three different items of cage furniture on the behaviour of male C57BL/6J mice in the plus-maze test. Animal Welfare 19(4), 401-409.

The aim of this study was to assess the effects of specific regimens of enrichment on the behaviour of C57BL/6J mice in the elevated plus-maze test (EPM). A total of 192 male C57BL/6J mice were...

Li, W. J., Yu, H., Yang, J. M. et al. 2010. Anxiolytic effect of music exposure on BDNFMet/Met transgenic mice. Brain Research 1347, 71-79.

Brain-derived neurotrophic factor (BDNF) has been reported to play important roles in the modulation of anxiety, mood stabilizers, and pathophysiology of affective disorders. Recently, a single nucleotide polymorphism (SNP) in the BDNF gene (Val66Met) has...

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...

Reed, B., Hawkins, P., Latham, N. et al. 2008. Report of the 2006 RSPCA/UFAW Rodent Welfare Group meeting. Lab Animal 37(5), 216-222.

The RSPCA/UFAW Rodent Welfare Group holds a one-day meeting every autumn to discuss current welfare research and to exchange views on rodent welfare issues. A key aim of the group is to encourage people to...

Sharp, J. L., Zammit, T., Azar, T. A. et al. 2003. Are "by-stander" female Sprague-Dawley rats affected by experimental procedures? Contemporary Topics in Laboratory Animal Science 42(1), 19-28.

The objective of this study was to test the hypotheses that female rats are stressed by being in the same room as animals subjected to common husbandry and experimental procedures and that the level of...

Reinhardt, V. 1997. Training nonhuman primates to cooperate during handling procedures: A review. Animal Technology 48, 55-73.

Twenty-six reports provide detailed information of how primates can be trained to voluntarily cooperate - rather than resist - during blood collection, injection, topical drug application, blood pressure measurement, urine collection, and capture.