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. 
Mechelinck, M., Kupp, C., Krüger, J. C. et al. 2019. Oxygen inhalation improves postoperative survival in ketamine-xylazine anaesthetised rats: An observational study. PLOS ONE 14(12), e0226430.

A simple but reliable and safe anaesthetic procedure is required for surgical interventions in small rodents. Combined ketamine and xylazine injections are often used in rats for less invasive surgery, possibly with spontaneous breathing and...

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...

Colby, L. A., Nowland, M. H., Kennedy, L. H. 2019. Clinical Laboratory Animal Medicine: An Introduction (5th ed). Wiley-Blackwell, Ames, IA.

The revised fifth edition of Clinical Laboratory Animal Medicine: An Introduction is an accessible guide to basic information for conducting animal research safely and responsibly. It includes a review of the unique anatomic and physiologic...

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...

Jirkof, P., Rudeck, J., Lewejohann, L. 2019. Assessing affective state in laboratory rodents to promote animal welfare—What is the progress in applied refinement research? Animals 9(12), 1026.

In the past, there was a strong focus on avoiding or reducing negative animal welfare in animal experimentation. Recently, the importance of promoting positive animal welfare in laboratory animals has been highlighted. To ensure and...

Rowland, N. E., Toth, L. A. 2019. Analytic and interpretational pitfalls to measuring fecal corticosterone metabolites in laboratory rats and mice. Comparative Medicine 69(5), 337–349.

Minimization and alleviation of stress are generally viewed as desirable aspects of laboratory animal management and use. However, achieving that goal requires an unambiguous and valid measure of stress. Glucocorticoid concentrations are commonly used as...

McMillan, F. D. (ed). 2019. Mental Health and Well-being in Animals (2nd ed). CABI, Wallingford, UK.

This second edition is fully revised, expanded, and comprehensively updated with the most current knowledge about the full array of mental health issues seen in animals. Written by key opinion leaders, internationally-recognized experts and specialists...

Morano, R., Hoskins, O., Smith, B. L. et al. 2019. Loss of environmental enrichment elicits behavioral and physiological dysregulation in female rats. Frontiers in Behavioral Neuroscience 12, 287.

Chronic stress drives behavioral and physiological changes associated with numerous psychiatric disease states. In rodents, the vast majority of chronic stress models involve imposition of external stressors, whereas in humans stress is often driven by...

Makowska, I. J., Weary, D. M. 2019. A good life for laboratory rodents? ILAR Journal 60(3), 373-388.

Most would agree that animals in research should be spared “unnecessary” harm, pain, or distress, and there is also growing interest in providing animals with some form of environmental enrichment. But is this the standard...

Skinner, M., Ceuppens, P., White, P. et al. 2019. Social-housing and use of double-decker cages in rat telemetry studies. Journal of Pharmacological and Toxicological Methods 96, 87-94.

Rat telemetry is widely used for biomedical research purposes and is used routinely in early pre-clinical drug development to screen for the potential cardiovascular risk of candidate drugs. Historically, these studies have been conducted in...

Hemmer, B. M., Parrish, A. E., Wise, T. B. et al. 2019. Social vs. Nonsocial housing differentially affects perseverative behavior in rats (Ratus norvegicus). Animal Behavior and Cognition 6(3), 168–178.

Perseverance, also commonly referred to as grit or industriousness, is the continued effort exerted to complete goal-directed tasks. Many factors, such as stress, can contribute to perseverative behavior, but the role of sociality on perseverance...

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...

ter Horst, E. N., Krijnen, P. A. J., Flecknell, P. et al. 2018. Sufentanil–medetomidine anaesthesia compared with fentanyl/fluanisone–midazolam is associated with fewer ventricular arrhythmias and death during experimental myocardial infarction in rats and limits infarct size following reperfusion. Laboratory Animals 52(3), 271-279.

To improve infarct healing following myocardial infarction in humans, therapeutic interventions can be applied during the inflammatory response. Animal models are widely used to study this process. However, induction of MI in rodents is associated...

Schuster, C. J., Pang, D. S. J. 2018. Forced-air pre-warming prevents peri-anaesthetic hypothermia and shortens recovery in adult rats. Laboratory Animals 52(2), 142-151.

General anaesthesia disrupts thermoregulation in mammals, which can cause hypothermia. Decreases in core body temperature of 1℃ cause significant postoperative complications in humans, and peri-anaesthetic hypothermia in mice increases data variability, which can potentially increase...

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...

Hoffman, J. F., Fan, A. X., Neuendorf, E. H. et al. 2018. Hydrophobic sand versus metabolic cages: A comparison of urine collection methods for rats (Rattus norvegicus). JAALAS 57(1), 51-57.

A common method for urine collection from rats requires the use of a metabolic cage, thus exposing animals to extended periods of isolation in an unfamiliar cage with a wire-mesh floor. A new method involving...

Jones, S., Neville, V., Higgs, L. et al. 2018. Assessing animal affect: An automated and self-initiated judgement bias task based on natural investigative behaviour. Scientific Reports 8, 12400.

Scientific methods for assessing animal affect, especially affective valence (positivity or negativity), allow us to evaluate animal welfare and the effectiveness of 3Rs Refinements designed to improve wellbeing. Judgement bias tasks measure valence; however, task-training...

Read, H., Perry, R. 2018. A refinement to Schedule 1. Animal Technology and Welfare 17(2), 117-120.

There are varying methods used for animal restraint and angle of injection. It remains unclear whether one method is more accurate than others. The primary objectives were to examine whether inverted restraint of rats resulted...

Clarke, D., Ioannou, L. 2018. Introduction of gang caging for group housed rats. Animal Technology and Welfare 17(2), 136-137.

Using an existing gang cage designed for ferrets, we developed a version that would be suitable for housing rats. Caging consisted of 3 floors with a combined floor area of 11620m, connected by 2 ladders...

van Wijk, H., Crossman, L., Adjin-Tettey, G. et al. 2018. Advances in animal welfare and scientific outcomes of the bile duct cannulated rat model utilised in ADME studies. Animal Technology and Welfare 17(1), 64-67.

Since rats lack a gall bladder, they are an ideal model for investigating continuous biliary excretion and biotransformation. The design and implementation of a modified tail cuff and cannula system introduced at Covance permits the...

Arakawa, H. 2018. Ethological approach to social isolation effects in behavioral studies of laboratory rodents. Behavioural Brain Research 341, 98-108.

The aim of the present review is to discuss how housing conditions affect behavioral performance in laboratory rodents from an ethological view. Commonly used laboratory rodents such as rats and mice, are originally captured animals...

Sikora, M., Nicolas, C., Istin, M. et al. 2018. Generalization of effects of environmental enrichment on seeking for different classes of drugs of abuse. Behavioural Brain Research 341, 109-113.

Background: Addiction is a chronic disease characterized by persistent vulnerability to relapse during abstinence. In animal models of addiction, accumulating evidence suggests that exposure to environmental enrichment (EE) during periods of abstinence can have curative...

Wang, R., Hausknechta, K. A., Haj-Dahmane, S. et al. 2018. Decreased environmental complexity during development impairs habituation of reinforcer effectiveness of sensory stimuli. Behavioural Brain Research 337, 53-60.

Previous research has shown that rats reared in simple/impoverished environments demonstrate greater repetitive responding for sensory reinforcers (e.g., light onset). Moreover, the brains of these rats are abnormally developed, compared to brains of rats reared...

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...