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. 
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...

Abela, C. 2020. Alternative training method using a mouse simulator in intravenous lateral tail vein procedures. Animal Technology and Welfare 19(3), 249-250.

The purpose of this study was to reduce or replace mouse cadavers for use in procedural training. All participants had mixed experience in various technical procedures such as oral gavage, intraperitoneal injections, etc., but none...

Van Wijk, H., Haida, D., Duncan, C. et al. 2020. Surgery refinements improve success rates in rat bile collection. Animal Technology and Welfare 19(3), 251-254.

This poster compares the model success rates using 2 different housing regimes during recovery from surgery. Catheters were placed in the bile duct to collect bile; a second catheter was secured into the duodenum where...

Rufiange, M., Leung, V. S.Y., Simpson, K. et al. 2020. Prewarming followed by active warming is superior to passive warming in preventing hypothermia for short procedures in adult rats (Rattus norvegicus) under isoflurane anesthesia. JAALAS 59(4), 377-383.

General anesthesia is a common procedure in laboratory rats; however, it impairs thermoregulation, rapidly leading to hypothermia as warm core blood is distributed to the cooler periphery. The protective strategy of prewarming before the onset...

Klune, C. B., Robbins, H. N. K., Leung, V. et al. 2020. Hypothermia during general anesthesia interferes with pain assessment in laboratory rats (Rattus norvegicus). JAALAS 59(6), 719-725.

Accurate pain assessment methods are necessary to ensure animal welfare and reliable data collection in animal research. The Rat Grimace Scale (RGS), a facial expression pain scale, allows effective identification of pain. However, the potential...

Scarborough, J., Mueller, F., Arban, R. et al. 2020. Preclinical validation of the micropipette-guided drug administration (MDA) method in the maternal immune activation model of neurodevelopmental disorders. Brain, Behavior, and Immunity 88, 461-470.

Pharmacological treatments in laboratory rodents remain a cornerstone of preclinical psychopharmacological research and drug development. There are numerous ways in which acute or chronic pharmacological treatments can be implemented, with each method having certain advantages...

Gjendal, K., Kiersgaard, M. K., Abelson, K. et al. 2020. Comparison of sublingual, facial and retro-bulbar blood sampling in mice in relation to animal welfare and blood quality. Journal of Pharmacological and Toxicological Methods 103, 106680.

Introduction: Repeated blood sampling is a common procedure in laboratory mice, but at present it is unknown which technique has the least impact on the animals when large or repeated blood samples are required. Retro-bulbar...

Woodard, C. L., Nasrallah, W. B., Samiei, B. V. et al. 2020. PiDose: An open-source system for accurate and automated oral drug administration to group-housed mice. Scientific Reports 10, 11584.

Drug treatment studies in laboratory mice typically employ manual administration methods such as injection or gavage, which can be time-consuming to perform over long periods and cause substantial stress in animals. These stress responses may...

McKay, L., Hunninck, L., Sheriff, M. 2020. A field-based adaptation of the classic morris water maze to assess learning and memory in a free-living animal. Animal Behavior and Cognition 9(4), 396–407.

Free-living animals rely on cognitive functions, such as learning and memory, for numerous aspects of their survival. However, research involving these mechanisms is often limited to the laboratory where animals are far removed from natural...

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...

Thomson, J., Mungall, W. 2019. Using subcuticular stitching in rats to replace skin closure clips as a refinement. Animal Technology and Welfare 18(1), 75-76.

Skin closure clips are widely used within the University of Edinburgh to close incision sites for various procedures in both rats and mice. In rats the skin closure clips very often come out as a...

Sørensen, D. B., Metzdorff, S. B., Jensen, L. K. et al. 2019. Time-dependent pathologic and inflammatory consequences of various blood sampling techniques in mice. JAALAS 58(3), 362-372.

We compared 6 frequently used mouse blood-sampling methods (lateral tail incision; tail-tip amputation; sublingual, submandibular, and saphenous vein puncture; and retrobulbar sinus puncture during isoflurane anesthesia) with regard to induction of local and systemic inflammation...

Dutton III, J. W., Artwohl, J. E., Huang, X. et al. 2019. Assessment of pain associated with the injection of sodium pentobarbital in laboratory mice (Mus musculus). JAALAS 58(3), 373-379.

The AVMA Guidelines for the Euthanasia of Animals considers injection of barbiturates to be an acceptable method of euthanasia in rodents but states there is a potential for pain when administered intraperitoneally. This study examined...

Falkenberg, M. K., Teilmann, A. C., Henriksen, T. et al. 2019. Clinical, physiologic, and behavioral evaluation of permanently catheterized NMRI mice. JAALAS 58(3), 380-389.

Vascular catheterization is becoming a popular technique in laboratory rodents, facilitating repetitive blood sampling and infusion in individual animals. In mice, catheterization is complicated by their small body size, which may increase the risk of...

Moffitt, A. D., Brignolo, L. L., Ardeshir, A. et al. 2019. The role of emotional contagion in the distress exhibited by grouped mice exposed to CO2. JAALAS 58(4), 430-437.

The 2013 AVMA Guidelines for the Euthanasia of Animals recommends a chamber volume displacement rate of 10% to 30% per minute (v/min) when euthanizing small laboratory rodents with CO2. Group euthanasia of mice is a...

Nosaka, N., Crother, T. R., Chen, S. et al. 2019. Optimal tube length of orotracheal intubation for mice. Laboratory Animals 53(1), 79–83.

Endotracheal tube (ETT) management is an essential technique in handling mice with mechanical ventilators. Malposition into bronchi causes not only lethal complications for them but also less efficient mechanical ventilation. However, in general, it is...

Gjendal, K., Lund Ottesen, J., Olsson, I. A. S. et al. 2019. Burrowing and nest building activity in mice after exposure to grid floor, isoflurane or ip injections. Physiology & Behavior 206, 59-66.

Burrowing and nest building are examples of highly motivated innate behaviours in rodents. Assessments based on these behaviours can be used as non-invasive indicators of pain, distress and suffering. In this study, we investigated the...

Koski, S. K., Leino, S., Rannanpää, S. et al. 2019. Implementation of improved postoperative care decreases the mortality rate of operated mice after an abundant 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons. Scandinavian Journal of Laboratory Animal Science 45(1).

A mouse model of Parkinson’s disease with an abundant lesion of nigrostriatal dopaminergic neurons can be achieved by stereotactic injection of 6-hydroxydopamine into the medial forebrain bundle. However, postoperative mortality can be excessively high without...

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...

Kaye, N. 2019. A technologist-led approach to altering the culture of care regarding blood sampling. Animal Technology and Welfare 18(3), 213-216.

This poster will describe the implementation by Animal Technologists and Named Persons of a well published refined bleeding technique. Establishing The Francis Crick Institute from legacy institutes required a standardised approach for many techniques, including...

Ritchie, A., Collier, P., Clare, P. et al. 2019. Food for thought: The development of drug loaded diets improve both science and welfare. Animal Technology and Welfare 18(3), 222-224.

In our facility, we use several hormone dependent tumour models with supplementation delivered via slow release subcutaneously implanted pellets, implanted via trochar. For example, breast tumours which rely on 17-β-Estradiol. Administration of E2 supplementation can...

Gent, T. C., Detotto, C., Vyssotski, A. L. et al. 2018. Epileptiform activity during inert gas euthanasia of mice. PLOS ONE 13(4), e0195872.

Carbon dioxide (CO2) is one of the most commonly used euthanasia agents for mice, yet it is highly aversive and nociceptive. Inert gases are a possible alternative, however there are qualitative reports of seizures resulting...

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...

Harikrishnan, V. S., Hansen, A. K., Abelson, K. S. P. et al. 2018. A comparison of various methods of blood sampling in mice and rats: Effects on animal welfare. Laboratory Animals 52(3), 253-264.

This study was conducted to investigate the effects of blood sampling on animal welfare in a total of 60 NTac:SD rats and 72 C57BL/6NTac mice of both sexes. Blood was sampled either by sublingual vein...