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...

Champneys, T., Castaldo, G., Consuegra, S., et al. 2018. Density dependent changes in neophobia and stress-coping styles in the world’s oldest farmed fish. Royal Society Open Science 5(12), 181473.

Farmed fish are typically reared at densities much higher than those observed in the wild, but to what extent crowding results in abnormal behaviours that can impact welfare and stress coping styles is subject to...

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...

Köhler, A., Collymore, C., Finger-Baier, K. et al. 2017. Report of Workshop on Euthanasia for Zebrafish—A Matter of welfare and science. Zebrafish 14(6), 547-551.

The increasing importance of zebrafish as a biomedical model organism is reflected by the steadily growing number of publications and laboratories working with this species. Regulatory recommendations for euthanasia as issued in Directive 2010/63/EU are...

Lopez-Luna, J., Al-Jubouri, Q., Al-Nuaimy, W. et al. 2017. Reduction in activity by noxious chemical stimulation is ameliorated by immersion in analgesic drugs in zebrafish. Journal of Experimental Biology 220(8), 1451-1458.

Research has recently demonstrated that larval zebrafish show similar molecular responses to nociception to those of adults. Our study explored whether unprotected larval zebrafish exhibited altered behaviour after exposure to noxious chemicals and screened a...

Kluge, K., Larenza Menzies, M. P., Kloeppel, H. et al. 2017. Femoral and sciatic nerve blockades and incision site infiltration in rabbits undergoing stifle joint arthrotomy. Laboratory Animals 51(1), 54-64.

This study was designed to determine whether perineural injections of local anaesthetics decreases intraoperative nociception and improves postoperative analgesia in New Zealand White rabbits undergoing experimental stifle arthrotomy. All animals were anaesthetized using isoflurane and...

Jirkof, P. 2017. Side effects of pain and analgesia in animal experimentation. Lab Animal 46(4), 123-128.

This review highlights selected effects of untreated pain and of widely used analgesics such as opioids, non-steroid anti-inflammatory drugs and antipyretics, to illustrate the relevance of carefully planned, appropriate and controlled analgesia for greater reproducibility...

Walsh, J., Percival, A., Turner, P. 2017. Efficacy of blunt force trauma, a novel mechanical cervical dislocation device, and a non-penetrating captive bolt device for on-farm euthanasia of pre-weaned kits, growers, and adult commercial meat rabbits. Animals 7(12), 100.

The commercial meat rabbit industry is without validated on-farm euthanasia methods, potentially resulting in inadequate euthanasia protocols. We evaluated blunt force trauma (BFT), a mechanical cervical dislocation device (MCD), and a non-penetrating captive bolt device...

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...

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...

Martin-Flores, M., Singh, B., Walsh, C. A. 2017. Effects of buprenorphine, methylnaltrexone, and their combination on gastrointestinal transit in healthy New Zealand White rabbits. JAALAS 56(2), 155-159.

Among the many analgesic agents available, buprenorphine appears to be the analgesic used most often in rabbits. Unfortunately, deleterious side effects of opioids, such as gastrointestinal stasis and anorexia, may discourage the use of these...

Cary, C. D., Lukovsky-Akhsanov, N. L., Gallardo-Romero, N. F. et al. 2017. Pharmacokinetic profiles of meloxicam and sustained-release buprenorphine in prairie dogs (Cynomys ludovicianus). JAALAS 56(2), 160-165.

In this study, we evaluated the pharmacokinetic profiles of meloxicam and sustained-release (SR) buprenorphine in prairie dogs. The 4 treatment groups were: low-dose meloxicam (0.2 mg/kg SC), high-dose meloxicam (4 mg/kg SC), low-dose buprenorphine SR...

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...

Polissidis, A., Zelelak, S., Nikita, M. et al. 2017. Assessing the exploratory and anxiety-related behaviors of mice. Do different caging systems affect the outcome of behavioral tests? Physiology & Behavior 177, 68-73.

Ample studies have shown that housing can affect the health, welfare and behavior of mice and therefore, the outcomes of certain experiments. The aim of this study was to investigate if three widely used housing...

Ferguson, R. 3Rs improvements in the Bexsero® (Meningitis B) vaccine. Animal Technology and Welfare 16(2), 150-152.

Bexsero® is a new vaccine in the UK which since September 2015 has been added to the childhood immunisation programme for the prevention of Meningitis B. The in-vivo test as performed in Biological Services Division...

Mortell, D., Moores, S. 2017. Increasing survival rates in the Zebrafish (Zebra danio) at the University of Manchester. Animal Technology and Welfare 16(3), 214-215.

The average survival rate for our Zebrafish (ZF) embryos was 65%. When it was time to create our next generation of Wild Type (WT) (used for embryo production), we decided to run a trial focussing...

Lopez-Luna, J., Canty, M. N., Al-Jubouri, Q. et al. 2017. Behavioural responses of fish larvae modulated by analgesic drugs after a stress exposure. Applied Animal Behaviour Science 195, 115-120.

Fish are known to respond to a wide range of irritant chemicals, displaying clear behavioural changes after exposure to potentially noxious stimuli. Recent evidence shows that these agents can have an impact on larval forms...

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...

Lopez-Luna, J., Al-Jubouri, Q., Al-Nuaimy, W. et al. 2017. Impact of analgesic drugs on the behavioural responses of larval zebrafish to potentially noxious temperatures. Applied Animal Behaviour Science 188, 97-105.

Recent studies have demonstrated that fish exhibit behavioural responses to noxious stimuli, including mechanical, chemical or thermal stimulation. In many cases, these responses are characterised by a reduction in the locomotor activity, which in turn...

Schroeder, P. G., Sneddon, L. U. 2017. Exploring the efficacy of immersion analgesics in zebrafish using an integrative approach. Applied Animal Behaviour Science 187, 93-102.

Home Office guidelines recommend the use of analgesics for all protected species, including fish during scientific procedures likely to result in pain, suffering, distress and lasting harm. In larger fish species some drugs have shown...

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...

Bermejo-Poza, R., De la Fuente, J., Pérez, C. 2016. Reducing the effect of pre-slaughter fasting on the stress response of rainbow trout (Oncorhynchus mykiss). Animal Welfare 25(3), 339-346.

Fasting is commonly used in aquaculture to empty the gut before slaughter, but little is known about how feeding frequency before fasting affects the stress response of trout. To find out more, 240 rainbow trout...

Jeger, V., Hauffe, T., Nicholls-Vuille, F. et al. 2016. Analgesia in clinically relevant rodent models of sepsis. Laboratory Animals 50(6), 418-426.

Postoperative analgesia in rodent sepsis models has been considerably neglected in the past. However, intentions to model clinical practice, increasing awareness of animal ethics, efforts to apply the 3Rs (replacement, reduction, refinement), and stricter legislation...

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)...