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. 
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...

Okabe, S., Takayanagi, Y., Yoshida, M. et al. 2020. Gentle stroking stimuli induce affiliative responsiveness to humans in male rats. Scientific Reports 10, 9135.

Gentle tactile stimuli have been shown to play an important role in the establishment and maintenance of affiliative social interactions. Oxytocin has also been shown to have similar actions. We investigated the effects of gentle...

Hambrecht, S., Oerke, A.‐K., Heistermann, M. et al. 2020. Diurnal variation of salivary cortisol in captive African elephants (Loxodonta africana) under routine management conditions and in relation to a translocation event. Zoo Biology 39(3), 186–196.

The present study assessed the diurnal variation in salivary cortisol in captive African elephants during routine management (baseline) and in relation to a potential stressor (translocation) to evaluate to what extent acute stress may affect...

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...

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...

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...

Kulkarni, S., Hickman, D. 2020. Isoflurane and carbon dioxide elicit similar behavioral responses in rats. Animals 10(8), 1431.

Euthanasia in rodents is an ongoing topic of debate due to concerns regarding the aversive nature of gases with anesthetic properties such as carbon dioxide (CO2) and isoflurane. The aim of this study was to...

LaFollette, M. R., Cloutier, S., Brady, C. M. et al. 2020. Changing human behavior to improve animal welfare: A longitudinal investigation of training laboratory animal personnel about heterospecific play or “rat tickling”. Animals 10(8), 1435.

Despite evidence for rat tickling’s animal welfare benefits, the technique is rarely implemented in part because of a lack of training. This study’s purpose was to determine the efficacy of online-only or online + hands-on...

Rault, J.-L., Waiblinger, S., Boivin, X. et al. 2020. The power of a positive human–animal relationship for animal welfare. Frontiers in Veterinary Science 7, 590867.

Domestic animals often seek and enjoy interacting with humans. Positive human–animal relationships can elicit positive emotions and other positive welfare outcomes. Nevertheless, our understanding of the underlying processes that govern the positive perception of humans...

Carlstead, K., Paris, S., Brown, J. L. et al. 2019. Good keeper-elephant relationships in North American zoos are mutually beneficial to welfare. Applied Animal Behaviour Science 211, 103-111.

Relationships between animals and their human caretakers can have profound impacts on animal welfare in farms, laboratories and zoos, while human attitudes are important predictors of caretaker behavior towards livestock. In this study, we examined...

Sherwen, S. L., Hemsworth, P. H. The visitor effect on zoo animals: Implications and opportunities for zoo animal welfare. Animals 9(6), 366.

Achieving and maintaining high standards of animal welfare is critical to the success of a modern zoo. Research has shown that an animal's welfare is highly dependent on how various individual animal factors (e.g., species...

Axiak Flammer, S., Eskes, C., Kohler, I. et al. 2019. Alternatives to carbon dioxide—Taking responsibility for humanely ending the life of animals. Animals 9(8), 482.

Carbon dioxide (CO2) is commonly used to kill rodents. However, a large body of research has now established that CO2 is aversive to them. A multidisciplinary symposium organized by the Swiss Federal Food Safety and...

Steiner, A. R., Axiak Flammer, S., Beausoleil, N. J. et al. 2019. Humanely ending the life of animals: Research priorities to identify alternatives to carbon dioxide. Animals 9(11), 911.

The use of carbon dioxide (CO2) for stunning and killing animals is considered to compromise welfare due to air hunger, anxiety, fear, and pain. Despite decades of research, no alternatives have so far been found...

Adams, R., Stanley, C. E., Piana, E. et al. 2019. Physiological and behavioral indicators to measure crustacean welfare. Animals 9(11), 914.

The purpose of this project was to determine how neural circuits were affected during warming by examining sensory neurons, the neuromuscular junction, and the cardiac function and behavior of the commercially important crustacean species, the...

Darbyshire, A. K., Oliver, K. H., Dupont, W. D. et al. 2019. Anesthesia and euthanasia of brine shrimp (Artemia franciscana). JAALAS 58(1), 58-63.

Invertebrates are often overlooked as laboratory animals, yet they are commonly used in toxicology, developmental, cellular and molecular biology, and radiation studies with euthanasia as an endpoint. Little is known regarding appropriate euthanasia methods for...

LaFollette, M. R., Cloutier, S., Brady, C. et al. 2019. Laboratory animal welfare and human attitudes: A cross-sectional survey on heterospecific play or “rat tickling”. PLOS ONE 14(8), e0220580.

Laboratory rat welfare is critically influenced by laboratory animal personnel through their implementation, or lack of implementation, of various enrichment techniques. One such promising technique is heterospecific play, or “rat tickling”, which mimics aspects of...

Crawley, J. A. H., Lahdenperä, M., Seltmann, M. W. et al. 2019. Investigating changes within the handling system of the largest semi-captive population of Asian elephants. PLOS ONE 14(1), e0209701.

The current extinction crisis leaves us increasingly reliant on captive populations to maintain vulnerable species. Approximately one third of Asian elephants (Elephas maximus) are living in semi-captive conditions in range countries. Their relationship with humans...

Améndola, L., Ratuski, A., Weary, D. M. 2019. Variation in the onset of CO2-induced anxiety in female Sprague Dawley rats. Scientific Reports 9, 19007.

Carbon dioxide (CO2) is commonly used to kill laboratory rats. Rats find CO2 aversive and aversion varies between individuals, indicating that rats vary in CO2 sensitivity. Healthy humans experience feelings of anxiety at concentrations similar...

Mather, J. A. 2019. Ethics and care: For animals, not just mammals. Animals 9(12), 1018.

Animals come in a huge array of types, species and structures, but without realizing it, we have focused our care on those like us, mammals. They look something like us, so it's easy to empathize...

Mazhary, H., Hawkins, P. 2019. Applying the 3Rs: A case study on evidence and perceptions relating to rat cage height in the UK. Animals 9(12), 1104.

This article investigates the barriers to implementing higher caging in animal research establishments in the UK. The use of animals in research and testing in the UK is regulated by the Animals (Scientific Procedures) Act...

Kells, N. J., Beausoleil, N. J., Sutherland, M. A. et al. 2018. Electroencephalographic responses of anaesthetised rats to carbon dioxide inhalation. Animal Welfare 27(3), 215-223.

Exposure to high concentrations of CO2 is a common means of stunning and killing laboratory rodents. However, there is concern regarding the potential for animals to have aversive experiences, such as pain or breathlessness, prior...

Khoo, S. Y.-S., Lay, B. P. P., Joya, J. et al. 2018. Local anaesthetic refinement of pentobarbital euthanasia reduces abdominal writhing without affecting immunohistochemical endpoints in rats. Laboratory Animals 52(2), 152-162.

Sodium pentobarbital is a commonly used agent for euthanizing laboratory rats, however its high pH can cause abdominal discomfort after intraperitoneal injection. Previous studies suggest that the addition of a local anaesthetic may alleviate this...

LaFollette, M. R., O’Haire, M. E., Cloutier, S. et al. 2018. A happier rat pack: The impacts of tickling pet store rats on human-animal interactions and rat welfare. Applied Animal Behaviour Science 203, 92-102.

Rats find initial interactions with humans frightening, which can lead to negative affect, and poor welfare. A handling technique called “tickling”, which mimics rat rough-and-tumble play, can be used to reduce these negative effects. When...

Weineck, K., Ray, A. J., Fleckenstein, L. J. et al. 2018. Physiological changes as a measure of crustacean welfare under different standardized stunning techniques: Cooling and electroshock. Animals 8(9), 158.

Stunning of edible crustaceans to reduce sensory perception prior and during slaughter is an important topic in animal welfare. The purpose of this project was to determine how neural circuits were affected during stunning by...