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. 
Štrbenc, M., Kuhar, U., Lainšček, D. et al. 2023. Rehoming and other refinements and replacement in procedures using golden hamsters in SARS-CoV-2 vaccine research. Animals 13(16), 2616.

Effective vaccines are needed to fight the COVID-19 pandemic. Forty golden hamsters were inoculated with two promising vaccine candidates and eighteen animals were used in pilot trials with viral challenge. ELISA assays were performed to...

Krall, C., Hopper, L. M., Hutchinson, E. K. 2023. Mice just want to have fun: Playpens facilitate faster training in non-invasive techniques for improved refinement and well-being. Laboratory Animal Science Professional 11(4) (July/August), 22-24.

Practical mechanisms that can be implemented by animal facilities to enhance refinement include the use of non-aversive handling, non-invasive alternative procedures, and additional environmental enrichment. Thus, we sought to collate these techniques by developing a...

Alizadeh, E. A., Graf, K., Schiwon, J. et al. 2023. Thirty years of telemetry-based data acquisition for cardiovascular drug safety evaluation: Applications and optimization. Journal of Pharmacological and Toxicological Methods 122, 107279.

Conducting safety evaluations of new drugs using conscious animals has been a specialty of our working group for thirty years. In this article, we review the various technical challenges and solutions dealt with over the...

Anderson, B. J., Curtis, A. M., Jen, A. et al. 2023. Plasma metabolomics supports non-fasted sampling for metabolic profiling across a spectrum of glucose tolerance in the Nile rat model for type 2 diabetes. Lab Animal 52(11), 269–277.

Type 2 diabetes is a challenge in modern healthcare, and animal models are necessary to identify underlying mechanisms. The Nile rat (Arvicanthis niloticus) develops diet-induced diabetes rapidly on a conventional rodent chow diet without genetic...

Brake, M. E., Russ, B. P., Gansebom, S. et al. 2023. Effects of extended-release buprenorphine on mouse models of influenza. Comparative Medicine 73(6), 466–473.

Mice are widely used as small animal models for influenza infection and immunization studies because of their susceptibility to many strains of influenza, obvious clinical signs of infection, and ease of handling. Analgesia is rarely...

Caires, C. R. S., Bossolani-Martins, A. L. 2023. Which form of environmental enrichment is most effective in rodent models of autism? Behavioural Processes 211, 104915.

Environmental enrichment (EE) is known to produce experience-dependent changes in the brains and behaviors of rodents, and it has therefore been widely used to study neurodevelopmental disorders, including autism. Current studies show significant protocol variation...

Fares, R., Champéroux, P. 2023. Simultaneous assessment of central nervous and respiratory systems using jacketed telemetry in socially-housed rats: Application of the “3Rs” principles in core battery safety pharmacology studies. Journal of Pharmacological and Toxicological Methods 121, 107268.

Central nervous (CNS) and respiratory systems are routinely investigated in safety pharmacology core battery studies. For small molecules, the assessment of both vital organ systems is frequently done in rats in two distinct studies. With...

Ferguson, L. T., Rashied, A. A., Liang, Z. et al. 2023. A novel scoring system for humane endpoints in mice with cecal ligation and puncture-induced sepsis. Comparative Medicine 73(6), 446–460.

Animal-based research is essential to the study of sepsis pathophysiology, diagnostics, and therapeutics. However, animal models of sepsis are often associated with high mortality because of the difficulty in predicting imminent death based on premortem...

George, A. J., O’Malley, C. I., Bulock, R. E. et al. 2023. Implementation of an alternative training method for cardiac blood collection in mice. JAALAS 62(6), 487–493.

Training personnel to work with animals presents a variety of challenges, both logistically and with regard to animal welfare. These issues make training an ideal opportunity to evaluate practices and to implement the 3R principles...

Lopez-Echeverria, G., Alamaw, E., Gorman, G. et al. 2023. Comparing three formulations of buprenorphine in an incisional pain model in mice. JAALAS 62(6), 531–537.

This study compared the therapeutic effects in mice of 3 different formulations of buprenorphine. These formulations were standard buprenorphine hydrochloride (Bup-HCL) and 2 different extended-release buprenorphine formulations (Bup-ER and Ethiqa-XR [Bup-XR]). Drugs were evaluated based...

Munro, B. A., Merenick, D. R., Gee, J. M. et al. 2023. Use of loss of righting reflex to assess susceptibility to carbon dioxide gas in three mouse strains. JAALAS 62(6), 553–558.

Exposure to CO2 gas is a common rodent euthanasia method. CO2 activates nociceptors in rats and is painful to humans at concentrations equal to or greater than 32.5% The concentration of CO2 at which rodents...

Nyqvist, D., Schiavon, A., Candiotto, A. et al. 2023. PIT-tagging Italian spined loach (Cobitis bilineata): Methodology, survival and behavioural effects. Journal of Fish Biology 102(3), 575–580.

The Italian spined loach (Cobitis bilineata) is an elongated, small-sized (

Hickman, D. L. 2023. Euthanasia of neonatal rats and mice using carbon monoxide. JAALAS 62(3), 274–278.

Minimization of potential pain and distress of rodents undergoing euthanasia is a touchstone of veterinary clinical medicine. Evaluation of this issue in postweanling rodents has supported revisions to the AVMA (American Veterinary Medical Association) Guidelines...

McNamara, A., Ballantine, A. R., Deuchande, R. et al. 2023. Comparison of fixed and rising displacement rates of CO2 for euthanasia of aged rats. JAALAS 62(5), 453–463.

This study compared euthanasia induced by rising concentrations of CO2 in aged rats (n = 59) using different gas displacement rates. Rats were preimplanted with cardiovascular telemetry devices and had been previously used for short...

Stuckey, J. E., Makhija, S. D., Reimer, D. C. et al. 2023. Effects of different grades of carbon dioxide on euthanasia of mice (Mus musculus). JAALAS 62(5), 430–437.

Carbon dioxide (CO2) is a conditionally acceptable method for mouse euthanasia, according to the American Veterinary Medical Association Guidelines for the Euthanasia of Animals. In a 2012 Office of Laboratory Animal Welfare (OLAW) webinar, representatives...

Hickman, D. L. 2022. Evaluation of carbon dioxide euthanasia of female Sprague Dawley rats alone or with unfamiliar conspecifics. JAALAS 61(2), 195-200.

Most studies evaluating methods of euthanasia to date have focused on the euthanasia of individual animals. However, larger chambers are commonly used to euthanize multiple cages of animals at once. This study evaluated the use...

Perret-Thiry, C., Raulic, J., Vergneau-Grosset, C. 2022. Evaluation of prolonged immersion in tricaine methanesulfonate for juvenile goldfish (Carassius auratus) euthanasia. Journal of the American Veterinary Medical Association 260(8), 911-915.

OBJECTIVE: Doses of buffered tricaine methanesulfonate (MS-222) up to 1000 mg/L for 15 minutes are reported inefficient to produce euthanasia in goldfish. The goal of this study was to determine if goldfish can be euthanized...

Berke, M. S., Fensholdt, L. K. D., Hestehave, S. et al. 2022. Effects of buprenorphine on model development in an adjuvant-induced monoarthritis rat model. PLOS ONE 17(1), e0260356.

Complete Freund’s adjuvant (CFA)-induced arthritis in rats is a common animal model for studying chronic inflammatory pain. However, modelling of the disease is associated with unnecessary pain and impaired animal wellbeing, particularly in the immediate...

Guillaumin, A., Vlcek, B., Wallén-Mackenzie, Å. 2022. Improving well-being and survival in the 6-OHDA lesion model of Parkinson´s disease in mice: Literature review and step-by-step protocol. Scandinavian Journal of Animal Science 48(1), 1-21.

Parkinson’s disease (PD) is the most common neurodegenerative motor disorder and primarily affects movement control but also a range of non-motor functions. With unknown etiology and lack of cure, much research is dedicated to unravel...

Williams, M. L., Torrini, L. A., Nolan, E. J. et al. 2022. Using classical and operant conditioning to train a shifting behavior in juvenile false water cobras (Hydrodynastes gigas). Animals 12(10), 1229.

All animals have the capacity to learn through operant conditioning and other types of learning, and as a result, zoos and other animal care facilities have shifted towards the use of positive reinforcement training to...

Knaebe, B., Weiss, C. C., Zimmermann, J. et al. 2022. The promise of behavioral tracking systems for advancing primate animal welfare. Animals 12(13), 1648.

Recent years have witnessed major advances in the ability of computerized systems to track the positions of animals as they move through large and unconstrained environments. These systems have so far been a great boon...

Hickman, D. L. 2022. Minimal exposure times for irreversible euthanasia with carbon dioxide in mice and rats. JAALAS 61(3), 283-286.

When using an anesthetic overdose to euthanize laboratory rodents, a secondary method of euthanasia is recommended to ensure that the apparent death is irreversible. This secondary method usually is accomplished through the collection of tissues...

McKinney, M. M., Dupont, W. D., Corson, K. J. et al. 2022. Physiologic and behavioral effects in mice anesthetized with isoflurane in a red-tinted or a traditional translucent chamber. JAALAS 61(4), 322-332.

Isoflurane has been characterized as a distressing agent for rodents, causing both physiologic and behavioral effects. Using a "darkened home cage" has been recommended during CO2 administration for rodent euthanasia; this is arguably a similar...

Fares, R., Flénet, T., Vial, J. et al. 2022. Non invasive jacketed telemetry in socially-housed rats for a combined assessment of respiratory system, electrocardiogram and activity using the DECRO system. Journal of Pharmacological and Toxicological Methods 117, 107195.

Respiratory and cardiovascular systems are among the vital organ systems that should be studied in safety pharmacology core battery test. Non-invasive jacketed external telemetry technology that enables concomitant monitoring of both systems has been available...

Van Assche, I. A., Padilla, M. S., Stupart, O. S. R. P. et al. 2022. Refinement of the stress-enhanced fear learning model of post-traumatic stress disorder: A behavioral and molecular analysis. Lab Animal 51(11), 293-300.

Post-traumatic stress disorder (PTSD) is a debilitating mental health condition for which current treatments have long-term efficacy in 50% of patients. There is a clear need for better understanding of the mechanisms underlying PTSD and...