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. 
Creamer-Hente, M. A., Lao, F. K., Dragos, Z. P. et al. 2018. Sex- and strain-related differences in the stress response of mice to CO₂ euthanasia. JAALAS 57(5), 513–519.

The 2013 edition of the AVMA Guidelines for the Euthanasia of Animals recommends a 10% to 30% volume displacement rate (VDR) per minute for CO2 euthanasia of rodents. Here we sought to evaluate behavior and...

Freret-Meurer, N. V., Alves, M. A. S. 2018. Personality in the longsnout seahorse, Hippocampus reidi Ginsburg, 1933: Are males shyer than females? Behavioural Processes 157, 106-110.

Individual responses, particularly based on personality, can have important consequences for individual fitness, based upon success in exploring new habitats, feeding on novel foods, and aggressiveness in competitive interactions. We conducted laboratory experiments to analyze...

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...

Chance, R. J., Cameron, G. A., Fordyce, M. et al. 2018. Effects of repeated anaesthesia on gill and general health of Atlantic salmon, Salmo salar. Journal of Fish Biology 93(6), 1069-1081.

Fish are the second most widely utilized vertebrate group used for scientific procedures in the United Kingdom, but the development and application of 3Rs (the principles of replacement, reduction, and refinement) in aquaculture disease research...

Coursodon, P., Cox, L., Largent-Milnes, T. M. et al. 2018. Enhanced environmental enrichment strategies for retired rhesus macaques. Laboratory Animal Science Professional 6(2) (June), 41-43.

One challenge in providing enrichment to NHP arises following completion of their assigned studies (retired) when there tends to be a sudden decrease in provision of daily human interaction and overall stimulation that results from...

Marquardt, N., Feja, M., Hünigen, H. et al. 2018. Euthanasia of laboratory mice: Are isoflurane and sevoflurane real alternatives to carbon dioxide? PLOS ONE 13(9), e0203793.

In the European Union (EU) millions of laboratory mice are used and killed for experimental and other scientific purposes each year. Although controversially discussed, the use of carbon dioxide (CO2) is still permitted for killing...

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...

Hopper, L. M., Cronin, K. A., Ross, S. R. 2018. A multi-institutional assessment of a short-form personality questionnaire for use with macaques. Zoo Biology 37(5), 281-289

There are two commonly used methods for calculating primates’ personality dimensions, behavioral assessments and surveys, which can be used separately or in conjunction. However, these methods have limitations. Behavioral assessments, such as the novel object...

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...

Nehete, P. N., Shelton, K. A., Nehete, B. P. et al. 2017. Effects of transportation, relocation, and acclimation on phenotypes and functional characteristics of peripheral blood lymphocytes in rhesus monkeys (Macaca mulatta). PLOS ONE 12(12), e0188694.

Nonhuman primates from domestic sources constitute a small, but critical, proportion of animals studied in research laboratories. Many of these nonhuman primates are raised at one facility and subsequently transported/relocated to another facility for research...

Boivin, G. P., Hickman, D. L., Creamer-Hente, M. A. et al. 2017. Review of CO2 as a euthanasia agent for laboratory rats and mice. JAALAS 56(5), 491-499.

Selecting an appropriate, effective euthanasia agent is controversial. Several recent publications provide clarity on the use of CO2 in laboratory rats and mice. This review examines previous studies on CO2 euthanasia and presents the current...

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...

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...

de Souza Dyer, C., Brice, A. K., Marx, J. O. 2017. Intraperitoneal administration of ethanol as a means of euthanasia for neonatal mice (Mus musculus). JAALAS 56(3), 299-306.

The humane euthanasia of animals in research is of paramount importance. Neonatal mice frequently respond differently to euthanasia agents when compared with adults. The AVMA's Guidelines for the Euthanasia of Animals includes intraperitoneal injection of...

Chinnadurai, S. K., Johnson III, J. G., Langan, J. N. 2017. Comparison of 3 methods for preventing perianesthetic hypothermia in callimicos (Callimico goeldii). JAALAS 56(3), 318-321.

Perianesthetic hypothermia is one of the most common complications in veterinary anesthesia, especially in small patients with a large body surface area to mass ratio. During anesthesia, body heat can be lost through 4 mechanisms—radiation...

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...

Boivin, G. P., Bottomley, M. A., Schiml, P. A. et al. 2017. Physiologic, behavioral, and histologic responses to various euthanasia methods in C57BL/6NTac male mice. JAALAS 56(1), 69-78.

Rodent euthanasia using exposure to increasing concentrations of CO2 has come under scrutiny due to concerns of potential pain during the euthanasia process. Alternatives to CO2, such as isoflurane and barbiturates, have been proposed as...

Cinque, C., De Marco, A., Mairesse, J. et al. 2017. Relocation stress induces short-term fecal cortisol increase in Tonkean macaques (Macaca tonkeana). Primates 58(2), 315-321.

The level of glucocorticoids, especially if obtained from noninvasive sampling, can be used as an index of animal well-being, allowing evaluation of the animal’s response to environmental modifications. Despite evidence that these hormones play a...

Phillips, B. E., Posner, L. P., Lewbart, G. A. et al. 2017. Effects of alfaxalone administered intravenously to healthy yearling loggerhead sea turtles (Caretta caretta) at three different doses. Journal of the American Veterinary Medical Association 250(8), 909-917.

OBJECTIVE To compare physiologic and anesthetic effects of alfaxalone administered IV to yearling loggerhead sea turtles (Caretta caretta) at 3 different doses. DESIGN Randomized crossover study. ANIMALS 9 healthy yearling loggerhead sea turtles. PROCEDURES Animals...

Guedes, S. R., Valentim, A. M., Antunes, L. M. 2017. Mice aversion to sevoflurane, isoflurane and carbon dioxide using an approach-avoidance task. Applied Animal Behaviour Science 189, 91-97.

Euthanasia of laboratory animals is one of the main concerns for animal welfare, especially the use of carbon dioxide (CO2) which has been described to induce aversive-like behaviours. In order to refine mass euthanasia in...

Stevens, C. H., Croft, D. P., Paull, G. C. et al. 2017. Stress and welfare in ornamental fishes: What can be learned from aquaculture? Journal of Fish Biology 91(2), 409-428.

The ornamental fish trade is estimated to handle up to 1.5 billion fishes. Transportation and handling of fishes imposes a range of stressors that can result in mortality at rates of up to 73%. Given...

Monreal-Pawlowsky, T., Marco-Cabedo, V., Manteca, X. et al. 2017. Environmental enrichment facilitates release and survival of an injured loggerhead sea turtle (Caretta caretta) after ten years in captivity. Journal of Zoo and Aquarium Research 5(4), 182-186.

In June 2006 a loggerhead sea turtle (Caretta caretta) was admitted to a rescue centre on the Mediterranean coast with severe fishing net entanglement in its fore right flipper. The flipper could not be saved...

Jolles, J. W., Aaron-Taylor, B., Manica, A. 2016. Recent social conditions affect boldness repeatability in individual sticklebacks. Animal Behaviour 112, 139-145.

Animal personalities are ubiquitous across the animal kingdom and have been shown both to influence individual behaviour in the social context and to be affected by it. However, little attention has been paid to possible...