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. 
Hwang, S.-K., Tyszkiewicz, C., Dragon, M. et al. 2022. Introduction of gloved hand to cage induces 22-kHz ultrasonic vocalizations in male albino rats. PLOS ONE 17(11), e0278034.

Rodents emit ultrasonic vocalizations (USVs) above the human hearing threshold of ~ 20 kHz to communicate emotional states and to coordinate their social interactive behavior. Twenty-two kHz USVs emitted by adult rats have been reported...

Novak, J., Jaric, I., Rosso, M. et al. 2022. Handling method affects measures of anxiety, but not chronic stress in mice. Scientific Reports 12(1), 20938.

Studies in mice have shown that less aversive handling methods (e.g. tunnel or cup handling) can reduce behavioural measures of anxiety in comparison to picking mice up by their tail. Despite such evidence, tail handling...

Assenmacher, C.-A., Lanza, M., Tarrant, J. C. et al. 2022. Post mortem study on the effects of routine handling and manipulation of laboratory mice. Animals 12(23), 3234.

Routine handling and manipulation of laboratory mice are integral components of most preclinical studies. Any type of handling and manipulation may cause stress and result in physical harm to mice, potentially leading to unintended consequences...

Hickman, D. L. 2021. Wellbeing of mice euthanized with carbon dioxide in their home cage as compared with an induction chamber. JAALAS 60(1), 72-76.

The AVMA Guidelines on Euthanasia state that, to decrease potential distress of animals, the home cage should be used for the euthanasia of mice. The current study evaluated this recommendation by comparing behavioral and physiologic...

Améndola, L., Ratuski, A., Weary, D. M. 2021. Individual differences in rat sensitivity to CO2. PLOS ONE 16(1), e0245347.

Feelings of fear, anxiety, dyspnea and panic when inhaling carbon dioxide (CO2) are variable among humans, in part due to differences in CO2 sensitivity. Rat aversion to CO2 consistently varies between individuals; this variation in...

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...

Stevens, C., Hawkins, P., Smulders, T. V. et al. 2021. Report of the 2020 RSPCA/UFAW rodent and rabbit welfare meeting. Animal Technology and Welfare 20(1), 21-33.

The RSPCA/UFAW rodent and rabbit welfare group has held a one-day meeting every autumn for the last 27 years, so that its members can discuss current welfare research, exchange views on welfare issues and share...

Bombail, V., Brown, S. M., Hammond, T. J. et al. 2021. Crying with laughter: Adapting the tickling protocol to address individual differences among rats in their response to playful handling. Frontiers in Veterinary Science 8, 677872.

In this Opinion paper, we consider whether current methods of tickling overemphasize the use of pinning (Figure 1) to which there may be a wider response variation than commonly acknowledged. We do not dispute that...

Song, M. K., Lee, J. H., Kim, Y.-J. 2021. Effect of chronic handling and social isolation on emotion and cognition in adolescent rats. Physiology & Behavior 237, 113440.

Adolescence is a critical period of establishing social relations through social interactions that affect the emotional development associated with stress responses, anxiety, depression, and cognitive development. We investigated the behavioral and neurobiological changes induced by...

Moore, J., Wickert, M. 2021. Thinking outside of the tunnel for non-aversive mouse handling. Animal Technology and Welfare 20(2), 161-163.

The key to non-aversive methods of handling lies in understanding what capture method creates the least anxiety in mice: be this tunnel or cupping or another method. It is important that we do not get...

Rodriguez-Sanchez, R., Barnaby, E., Améndola, L. et al. 2021. Voluntary oral ingestion of a sedative prior to euthanasia with CO2: Behavioural responses of mice. Animals 11(10), 2879.

Laboratory mice are commonly euthanised with carbon dioxide (CO2); however, there is ample evidence that this gas is aversive. Previous work suggests that sedation achieved via injection with benzodiazepines prior to CO2 administration could reduce...

Brunt, M. W., Améndola, L., Weary, D. M. 2021. Attitudes of laboratory animal professionals and researchers towards carbon dioxide euthanasia for rodents and perceived barriers to change. Laboratory Animals 55(6), 531-539.

Evidence indicates that carbon dioxide (CO2) induces negative affective states (including anxiety, fear and distress) in laboratory rodents, but many countries still accept it for euthanasia. Alternative methods (e.g. inhalant anaesthetic) may represent a refinement...

Redaelli, V., Bosi, A., Luzi, F. et al. 2021. Neuroinflammation, body temperature and behavioural changes in CD1 male mice undergoing acute restraint stress: An exploratory study. PLOS ONE 16(11), e0259938.

Background: Animal models used to study pathologies requiring rehabilitation therapy, such as cardiovascular and neurologic disorders or oncologic disease, must be as refined and translationally relevant as possible. Sometimes, however, experimental procedures such as those...

Sandgren, R., Grims, C., Waters, J. et al. 2021. Using cage ladders as a handling device reduces aversion and anxiety in laboratory mice, similar to tunnel handling. Scandinavian Journal of Laboratory Animal Science 47(5), 31-41.

Handling laboratory animals for husbandry and other procedures can be an important source of anxiety and stress, compromising animal welfare as well as the reliability of research that is sensitive to background stressors. Studies have...

Henderson, L. J., Smulders, T. V., Roughan, J. V. 2020. Identifying obstacles preventing the uptake of tunnel handling methods for laboratory mice: An international thematic survey. PLOS ONE 15(4), e0231454.

Handling of laboratory mice is essential for experiments and husbandry, but handling can increase anxiety in mice, compromising their welfare and potentially reducing replicability between studies. The use of non-aversive handling (e.g., tunnel handling or...

Ueno, H., Takahashi, Y., Suemitsu, S. et al. 2020. Effects of repetitive gentle handling of male C57BL/6NCrl mice on comparative behavioural test results. Scientific Reports 10(1), 3509.

Mice are the most commonly used laboratory animals for studying diseases, behaviour, and pharmacology. Behavioural experiment battery aids in evaluating abnormal behaviour in mice. During behavioural experiments, mice frequently experience human contact. However, the effects...

Costa, R., Leite Tamascia, M., Sanches, A. et al. 2020. Tactile stimulation of adult rats modulates hormonal responses, depression-like behaviors, and memory impairment induced by chronic mild stress: Role of angiotensin II. Behavioural Brain Research 379, 112250.

Physical touch can help to decrease the effects of stress. The aim of this study was to evaluate the influence of tactile stimulation on the hormonal and behavioral responses of young adult rats submitted to...

Frost, K., Shah, M., Leung , V. S. Y. et al. 2020. Aversion to desflurane and isoflurane in Sprague-Dawley rats (Rattus norvegicus). Animals 10(6), 950.

Carbon dioxide and isoflurane are widely used for killing rats, yet may not truly achieve “euthanasia”, because they elicit aversion. The inhalant anesthetic desflurane is faster acting than isoflurane, representing a potential refinement. Using an...

Thorpe, E. 2020. Alternative handling techniques to reduce anxiety in laboratory mice. Animal Technology and Welfare 19(1), 76-78.

Recent studies at Liverpool University have indicated that handling mice by their tails during routine cleaning and procedures induced aversion and high anxiety in many commonly used strains. The evidence from the Liverpool study suggests...

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...

Améndola, L., Weary, D. M. 2020. Understanding rat emotional responses to CO2. Translational Psychiatry 10, 253.

The aim of this review is to summarize evidence regarding rat emotional experiences during carbon dioxide (CO2) exposure. The studies reviewed show that CO2 exposure is aversive to rats, and that rats respond to CO2...

Turner, P. V., Hickman, D. L., van Luijk, J. et al. 2020. Welfare impact of carbon dioxide euthanasia on laboratory mice and rats: A systematic review. Frontiers in Veterinary Science 7, 411.

Background: There has been increased concern about the suitability of CO2 as a method for euthanasia of laboratory mice and rats, including the potential discomfort, pain or distress that animals may experience prior to loss...

Stevens, C., Finnegan, E., Clarkson, J. et al. 2020. Report of the 2019 RSPCA/UFAW Rodent Welfare meeting. Animal Technology and Welfare 19(2), 101-111.

The RSPCA/UFAW Rodent Welfare Group has held a one-day meeting every autumn for the last 26 years, so that its members can discuss current welfare research, exchange views on welfare issues, and share experiences of...

Shomer, N. H., Allen-Worthington, K. H., Hickman, D. L. et al. 2020. Review of rodent euthanasia methods. JAALAS 59(3), 242–253.

The optimal choice of euthanasia method for laboratory rodents depends on a number of factors, including the scientific goals of the study, the need to minimize animal pain and/or distress, applicable guidelines and laws, the...

Laferriere, C. A., Pang, D. S. 2020. Review of intraperitoneal injection of sodium pentobarbital as a method of euthanasia in laboratory rodents. JAALAS 59(3), 254–263.

Euthanasia is one of the most commonly performed procedures in biomedical research, involving tens of millions of animals in North America and Europe every year. The use of sodium pentobarbital, injected intraperitoneally, for killing rodents...