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. 
Ehrlich, O., Karamalakis, A., Krylov, A. J. et al. 2019. Clove oil and AQUI-S efficacy for zebrafish embryo, larva, and adult anesthesia. Zebrafish 16(5), 451-459.

Since the use of the zebrafish Danio rerio genetic model organism within the scientific research community continues to grow rapidly, continued procedural refinement to support high-quality, reproducible research and improve animal welfare remains an important...

Balko, J. A., Lindemann, D. M., Allender, M. C. et al. 2019. Evaluation of the anesthetic and cardiorespiratory effects of intramuscular alfaxalone administration and isoflurane in budgerigars (Melopsittacus undulatus) and comparison with manual restraint. Journal of the American Veterinary Medical Association 254(12), 1427-1435.

OBJECTIVE To evaluate the anesthetic and cardiorespiratory effects of IM alfaxalone and isoflurane administration in budgerigars (Melopsittacus undulatus) and compare use of these agents with use of manual restraint. ANIMALS 42 healthy budgerigars. PROCEDURES For...

Hankenson, F. C., Marx, J. O., Gordon, C. J. et al. 2018. Effects of rodent thermoregulation on animal models in the research environment. Comparative Medicine 68(6), 425–438.

To best promote animal wellbeing and the efficacy of biomedical models, scientific, husbandry, and veterinary professionals must consider the mechanisms, influences, and outcomes of rodent thermoregulation in contemporary research environments. Over the last 2 decades...

Hohlbaum, K., Bert, B., Dietze, S. et al. 2018. Impact of repeated anesthesia with ketamine and xylazine on the well-being of C57BL/6JRj mice. PLOS ONE 13(9), e0203559.

Within the scope of the 3Rs of Russel and Burch, the number of laboratory animals can be reduced by repeated use of an animal. This strategy only becomes relevant, if the total amount of pain...

Hohlbaum, K., Bert, B., Dietze, S. et al. 2017. Severity classification of repeated isoflurane anesthesia in C57BL/6JRj mice—Assessing the degree of distress. PLOS ONE 12(6), e0179588.

According to the EU Directive 2010/63, the severity of a procedure has to be classified as mild, moderate or severe. General anesthesia is thought to be mild, but the Directive does not differentiate between single...

Skorupski, A. M., Zhang, J., Ferguson, D. et al. 2017. Quantification of induced hypothermia from aseptic scrub applications during rodent surgery preparation. JAALAS 56(5), 562-569.

Laboratory mice (Mus musculus) are prone to develop hypothermia during anesthesia for surgery, thus potentially impeding anesthetic recovery, wound healing, and future health. The core body temperatures of isoflurane-anesthetized mice are influenced by the choice...

De Lombaert, M. C. M., Rick, E. L., Krugner-Higby, L. A. et al. 2017. Behavioral characteristics of adult zebrafish (Danio rerio) after MS222 anesthesia for fin excision. JAALAS 56(4), 377-381.

The health of laboratory animals is an ethical responsibility of researchers and a critical determinant of experimental outcome. Therefore, all Husbandry & Management procedures should be evaluated for their effects on mortality, behavior, and physiology...

Chatigny, F., Kamunde, C., Creighton, C. M. et al. 2017. Uses and doses of local anesthetics in fish, amphibians, and reptiles. JAALAS 56(3), 244-253.

Local anesthetics are an integral part of routine pain management in mammals, yet their use is relatively limited in fish, amphibians and reptiles. These animals frequently undergo potentially painful surgical procedures and therefore could possibly...

Reiter, C. P., Christy, A. C., Olsen, C. H. et al. 2017. Effect of home cage bedding in the induction chamber on serum cortisol and corticosterone levels in response to isoflurane-induced anesthesia in C57BL/6J mice. JAALAS 56(2), 118-121.

Mice are routinely anesthetized with isoflurane in an induction chamber. The AVMA Guidelines for the Euthanasia of Animals states that distress should be minimized during euthanasia but does not address this point in regard to...

Janssen, C. F., Maiello, P., Wright Jr, M. J. et al. 2017. Comparison of atipamezole with yohimbine for antagonism of xylazine in mice anesthetized with ketamine and xylazine. JAALAS 56(2), 142-147.

The α2 adrenergic agonist xylazine produces a sedative effect and is typically combined with ketamine and used for anesthesia or chemical restraint of laboratory mice. Xylazine's sedative effect—and its undesirable side effects of bradycardia, hypotension...

Wilding, L. A., Hampel, J. A., Khoury, B. M. et al. 2017. Benefits of 21% oxygen compared with 100% oxygen for delivery of isoflurane to mice (Mus musculus) and rats (Rattus norvegicus). JAALAS 56(2), 148-154.

At research institutions, isoflurane delivered by precision vaporizer to a face mask is the standard for rodent surgery and for procedures with durations that exceed a few minutes. Pure oxygen is often used as the...

Lidster, K., Readman, G. D., Prescott, M. J. et al. 2017. International survey on the use and welfare of zebrafish Danio rerio in research. Journal of Fish Biology 90(5), 1891-1905.

A survey was conducted regarding zebrafish Danio rerio use for scientific research with a focus on: anaesthesia and euthanasia; housing and husbandry; breeding and production; refinement opportunities. A total of 98 survey responses were received...

Martins, T., Valentim, A. M., Pereira, L. N. et al. 2016. Anaesthesia and analgesia in laboratory adult zebrafish: a question of refinement. Laboratory Animals 50(6), 476-488.

Anaesthesia is used daily in fish experimental procedures; however, the use of an inadequate anaesthetic protocol can compromise not only the animal’s welfare but also the reliability of results. The use of zebrafish (Danio rerio)...

Norton, W. B., Scavizzi, F., Smith, C. D. et al. 2016. Refinements for embryo implantation surgery in the mouse: Comparison of injectable and inhalant anesthesias – tribromoethanol, ketamine and isoflurane – on pregnancy and pup survival. Laboratory Animals 50(5), 335-343.

An essential aspect of genetically-engineered mice (GEM) is the ability to produce live animals after the appropriate injection procedure. Animals are produced by implantation of manipulated embryos into pseudopregnant females for gestation, parturition, and growth...

Mattheis, L., Jung, J.-S., Hiebl, B. et al. 2016. Perioperative support reduces mortality of obese BALB/c mice after ovariectomy. Lab Animal 45(7), 262-267.

The incidence of obesity is on the rise in most western countries and represents major risks to health. Obesity causes complex metabolic dysfunctions and can be associated with a large number of secondary diseases. To...

Miller, A., Kitson, G., Skalkoyannis, B. et al. 2015. The effect of isoflurane anaesthesia and buprenorphine on the mouse grimace scale and behaviour in CBA and DBA/2 mice. Applied Animal Behaviour Science 172, 58-62.

Prevention or alleviation of pain in laboratory mice is a fundamental requirement of in vivoresearch. The mouse grimace scale (MGS) has the potential to be an effective and rapid means of assessing pain and analgesic...

Cesarovic, N., Arras, M., Jirkof, P. 2014. Impact of inhalation anaesthesia, surgery and analgesic treatment on home cage behaviour in laboratory mice. Applied Animal Behaviour Science. 157, 137-145.

Anaesthesia and analgesia are used frequently in laboratory routine to ensure animal welfare and good scientific outcomes in experiments that may elicit pain or require immobilisation of the animal. However, there is concern regarding the...

Readman, G. D., Owen, S. F., Murrell, J. C. et al. 2013 Do fish perceive anaesthetics as aversive? PLOS ONE. 8(9), e73773.

This study addresses a fundamental question in fish welfare: are the anaesthetics used for fish aversive? Despite years of routine general use of many agents, within both scientific research and aquaculture, there is a paucity...

Branson, E. J. (Ed.) 2008. Fish Welfare. Blackwell Publishing Ltd: Oxford, UK, 300 p.

Fish have the same stress response and powers of nociception as mammals. Their behavioural responses to a variety of situations suggest a considerable ability for higher level neural processing – a level of consciousness equivalent...

Conour, L. A., Murray, K. A., Brown, M. J. 2006. Preparation of animals for research -- Issues to consider for rodents and rabbits. ILAR Journal 47(4), 283-293.

This article provides details to consider when preparing to use animals in biomedical research. The stress of transport and receipt of animals into a new environment mandate the need for a period of stabilization and...

Capitanio, J. P., Kyes, R. C., Fairbanks, L. A. 2006. Considerations in the selection and conditioning of Old World monkeys for laboratory research: Animals from domestic sources. ILAR Journal 47(4), 294-306.

Preparation of domestically bred animals for research usually involves some combination of social separation, relocation, resocialization, alterations in physical space, photoperiod, and diet, as well as exposure to novel environments. The research literature that has...

Tardif, S. D., Bales, K., Williams, L. et al. 2006. Preparing New World monkeys for laboratory research. ILAR Journal 47(4), 307-315.

New World monkeys represent an important but often poorly understood research resource. The relatively small size and low zoonotic risk of these animals make them appealing as research subjects in a number of areas. However...