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. 
Zevnik, B., Jerchow, B., Buch, T. 2022. 3R measures in facilities for the production of genetically modified rodents. Lab Animal 51(6), 162-177.

Sociocultural changes in the human–animal relationship have led to increasing demands for animal welfare in biomedical research. The 3R concept is the basis for bringing this demand into practice: Replace animal experiments with alternatives where...

Hughey, S., Campbell, D., Rapp-Santos, K. et al. 2022. Refining the rat sciatic nerve block: A novel ultrasound-guided technique. Laboratory Animals 56(2), 191-195.

Murine translational models are an important tool to understand pain pathophysiology. One procedure used frequently in murine research is the sciatic nerve block. This study sought to demonstrate the use of ultrasound-guided sciatic nerve block...

Clarkson, J. M., Martin, J. E., McKeegan, D. E. F. 2022. A review of methods used to kill laboratory rodents: Issues and opportunities. Laboratory Animals 56(5), 419-436.

Rodents are the most widely used species for scientific purposes. A critical pre-requisite of their use, based on utilitarian ethical reasoning, is the provision of a humane death when necessary for scientific or welfare grounds...

Allioux, C., Achaintre, L., Cheataini. F. et al. 2022. Animal welfare assessment after severe traumatic brain injury in rats. Laboratory Animals 56(6), 528-539.

Severe traumatic brain injury (TBI) is a multifactorial injury process involving respiratory, cardiovascular and immune functions in addition to the brain. Thus, live animal models are needed to study the molecular, cellular and systemic mechanisms...

Hwang, S.-K., Tyszkiewicz, C., Dragon, M. et al. 2022. Introduction of gloved hand to cage induces 22-kHz ultrasonic vocalizations in male albino rats. PLOS ONE 17(11), e0278034.

Rodents emit ultrasonic vocalizations (USVs) above the human hearing threshold of ~ 20 kHz to communicate emotional states and to coordinate their social interactive behavior. Twenty-two kHz USVs emitted by adult rats have been reported...

Córneo, E., Michels, M., Abatti, M. et al. 2022. Enriched environment causes epigenetic changes in hippocampus and improves long-term cognitive function in sepsis. Scientific Reports 12(1), 11529.

Sepsis is defined as a life-threatening organ dysfunction caused by an inappropriate host response to infection. The presence of oxidative stress and inflammatory mediators in sepsis leads to dysregulated gene expression, leading to a hyperinflammatory...

Chung, Y. H., Gulumian, M., Pleus, R. C. et al. 2022. Animal welfare considerations when conducting OECD test guideline inhalation and toxicokinetic studies for nanomaterials. Animals 12(23), 3305.

The OECD test guidelines for animal experiments play an important role in evaluating the chemical hazards. Animal tests performed using OECD guidelines, especially when the good laboratory practice (GLP) principle is applied, reduce the duplication...

Farag, A., Mandour, A. S., Hamabe, L. et al. 2022. Novel protocol to establish the myocardial infarction model in rats using a combination of medetomidine-midazolam-butorphanol (MMB) and atipamezole. Frontiers in Veterinary Science 9, 1064836.

Myocardial infarction (MI) is one of the most common cardiac problems causing deaths in humans. Previously validated anesthetic agents used in MI model establishment are currently controversial with severe restrictions because of ethical concerns. The...

Cait, J., Cait, A., Scott, R. W. et al. 2022. Conventional laboratory housing increases morbidity and mortality in research rodents: Results of a meta-analysis. BMC Biology 20(1), 15.

Over 120 million mice and rats are used annually in research, conventionally housed in shoebox-sized cages that restrict natural behaviours (e.g. nesting and burrowing). This can reduce physical fitness, impair thermoregulation and reduce welfare (e.g...

Hepps Keeney, C., Harrison, T. M. 2022. Euthanasia complications in non-domestic species. Journal of Zoological and Botanical Gardens 3(4), 616–623.

There are very few studies describing euthanasia complications in non-domestic species. The goal of this study was to survey veterinarians to determine what complications may commonly occur during the euthanasia of non-domestic species. An online...

Casey, K. M., Gore, F., Vilches-Moure, J. G. et al. 2021. Management of morbidity and mortality in a New Zealand white rabbit model of steroidinduced osteonecrosis of the femoral head. Comparative Medicine 71(1), 86-98.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a condition documented in humans and animals exposed to chronic steroid administration. The rabbit has become a preferred animal model for investigating the pathogenesis and treatment of...

Améndola, L., Ratuski, A., Weary, D. M. 2021. Individual differences in rat sensitivity to CO2. PLOS ONE 16(1), e0245347.

Feelings of fear, anxiety, dyspnea and panic when inhaling carbon dioxide (CO2) are variable among humans, in part due to differences in CO2 sensitivity. Rat aversion to CO2 consistently varies between individuals; this variation in...

Blaney, A., Jampachaisri, K., Huss, M. K. et al. 2021. Sustained release buprenorphine effectively attenuates postoperative hypersensitivity in an incisional pain model in neonatal rats (Rattus norvegicus). PLOS ONE 16(2), e0246213.

Despite the need for safe and effective postoperative analgesia in neonates, research regarding pain management in neonatal rodents is relatively limited. Here, we investigate whether sustained release buprenorphine (Bup SR) effectively attenuates thermal hypersensitivity in...

Carbone, L. 2021. Estimating mouse and rat use in American laboratories by extrapolation from Animal Welfare Act-regulated species. Scientific Reports 11(1), 493.

Alone among Western nations, the United States has a two-tier system for welfare protections for vertebrate animals in research. Because its Animal Welfare Act (AWA) excludes laboratory rats and mice (RM), government veterinarians do not...

Sørensen, D., Cloutier, S., Gaskill, B. (Eds.). 2021. Animal-centric Care and Management - Enhancing Refinement in Biomedical Research. CRC Press, Boca Raton, FL.

The concept of the 3Rs (Refinement, Reduction and Replacement) has been used as a framework for improving the welfare of laboratory animals for the last half century. By establishing an animal-centric view on housing and...

Silva-Reis, R., Faustino-Rocha, A. I., Gonçalves, M. et al. 2021. Refinement of animal model of colorectal carcinogenesis through the definition of novel humane endpoints. Animals 11(4), 985.

This study aimed to define appropriate humane endpoints (HEs) for an animal model of colorectal carcinogenesis (CRC). Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2) injected with ethylenediamine tetraacetic acid...

Bombail, V., Brown, S. M., Hammond, T. J. et al. 2021. Crying with laughter: Adapting the tickling protocol to address individual differences among rats in their response to playful handling. Frontiers in Veterinary Science 8, 677872.

In this Opinion paper, we consider whether current methods of tickling overemphasize the use of pinning (Figure 1) to which there may be a wider response variation than commonly acknowledged. We do not dispute that...

Krueger, L. D., Chang, S. E., Motoc, M. et al. 2021. Effects of pair housing on patency of jugular catheters in rats (Rattus norvegicus). JAALAS 60(3), 357-364.

Chronic vascular access devices are widely used in a variety of species for repeated blood sampling or substance administration. Jugular catheters are commonly used for studying addiction-related behaviors in rats. Rats with catheters have historically...

Learmonth, M. J., Sherwen, S., Hemsworth, P. 2021. Assessing choice ability and preferences of five Leopard Tortoises (Stigmochelys pardalis) for three stimuli through a novel two-phase preference test. Journal of Zoo and Aquarium Research, 9(2), 94-101.

Preference testing has long been used in ethology and animal welfare science to assess the preferences that animals have for different resources and stimuli. The study conducted herein assessed the choice-making ability of five leopard...

Komatsu, T., Ohta, H., Motegi, H. et al. 2021. A novel model of ischemia in rats with middle cerebral artery occlusion using a microcatheter and zirconia ball under fluoroscopy. Scientific Reports 11(1), 12806.

Here, we present a highly selective rat MCAO model by percutaneous caudal arterial puncture using a microcatheter and zirconia ball under fluoroscopic guidance. The model is predictable and reproducible, which is well confined within the...

Learmonth, M. J., Sherwen, S., Hemsworth, P. H. 2021. Assessing preferences of two zoo-housed Aldabran giant tortoises (Aldabrachelys gigantea) for three stimuli using a novel preference test. Zoo Biology 40(2), 98-106.

Recent research has uncovered many complex cognitive traits and affective processes in many reptile species, such as the ability to make choices that are rewarding or pleasurable. The investigation herein was initiated after many years...

Kay, W. R., Mawson, P. R. 2021. An efficient method for the euthanasia of cane toads (Rhinella marina) under northern Australian field conditions. Animals 11(8), 2239.

The euthanasia of cane toads under field conditions presents a number of logistical and animal welfare challenges. One recommended method of control involves the use of carbon dioxide in plastic bags. This paper describes the...

Bennett, T. E., Pavek, T. J., Schwark, W. S. et al. 2021. Comparison of nociceptive effects of buprenorphine, firocoxib, and meloxicam in a plantar incision model in Sprague–Dawley rats. JAALAS 60(5), 539-548.

Due to their reduced frequency of dosing and ease of availability, NSAIDs are generally preferred over opioids for rodent analgesia. We evaluated the efficacy of the highly COX2-selective NSAID firocoxib as compared with meloxicam and...

Brunt, M. W., Améndola, L., Weary, D. M. 2021. Attitudes of laboratory animal professionals and researchers towards carbon dioxide euthanasia for rodents and perceived barriers to change. Laboratory Animals 55(6), 531-539.

Evidence indicates that carbon dioxide (CO2) induces negative affective states (including anxiety, fear and distress) in laboratory rodents, but many countries still accept it for euthanasia. Alternative methods (e.g. inhalant anaesthetic) may represent a refinement...

Costa, R., Leite Tamascia, M., Sanches, A. et al. 2020. Tactile stimulation of adult rats modulates hormonal responses, depression-like behaviors, and memory impairment induced by chronic mild stress: Role of angiotensin II. Behavioural Brain Research 379, 112250.

Physical touch can help to decrease the effects of stress. The aim of this study was to evaluate the influence of tactile stimulation on the hormonal and behavioral responses of young adult rats submitted to...