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. 
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...

Gardhouse, S., Beaufrere, H., Hawkins, M. G. et al. 2023. Evaluation of oral transmucosal administration of pentobarbital for euthanasia of conscious wild birds. Journal of Applied Animal Welfare Science 26(1), 4–14.

This prospective study evaluated oral transmucosal pentobarbital sodium at three doses in 110 wild-caught wild birds requiring euthanasia. Birds received transmucosal pentobarbital at five (430 mg/kg), six (516 mg/kg), and seven times (602 mg/kg) the...

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...

Miguelena Chamorro, B., Swaminathan, G., Mundt, E. et al. 2023. Towards more translatable research: Exploring alternatives to gavage as the oral administration route of vaccines in rodents for improved animal welfare and human relevance. Lab Animal 52(9), 195–197.

Oral vaccines are gaining attention for their ease of administration and ability to activate mucosal immune responses. However, preclinical studies using this route often require the use of gavage, which has limitations. In this comment...

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...

Psarou, E., Vezoli, J., Schölvinck, M. L. et al. 2023. Modular, cement-free, customized headpost and connector-chamber implants for macaques. Journal of Neuroscience Methods 393, 109899.

Background: Neurophysiological studies with awake macaques typically require chronic cranial implants. Headpost and connector-chamber implants are used to allow head stabilization and to house connectors of chronically implanted electrodes, respectively. New method: We present long-lasting...

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...

Riddell, D. L., Hyndman, T. H., Bowden, R. S. et al. 2023. Use of a low-calorie flavored gel to facilitate oral self-administration of analgesics in mice. JAALAS 62(2), 163–169.

The goals of this study were to determine whether mice would adapt to a low-calorie flavored water gel as their sole source of hydration and whether the addition of acetaminophen, tramadol, meloxicam, or buprenorphine to...

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...

Martins, T., Matos, A. F., Soares, J. et al. 2022. Comparison of gelatin flavors for oral dosing of C57BL/6J and FVB/N mice. JAALAS 61(1), 89-95.

Precise oral dosing in rodents is usually achieved by intragastric gavage. If performed incorrectly due to technical difficulties, inexperience, or animal resistance, oral gavage may have animal welfare implications such as esophageal and gastric rupture...

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...

Guerrero-Martin, S. M., Brill, S., Carlson, B. W. 2022. Development and implementation of a positive reinforcement training program for nonhuman primates in biomedical research. Laboratory Animal Science Professional 10(1) (January/February), 48-52.

Despite clear benefits of PRT for NHPs and biomedical research, investigators often view the investment in personnel expertise and time required to train animals as deterrents towards adopting PRT. We provide an example of how...

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...

Bartlett, J., Davies, J., Purawijaya, D. et al. 2022. Refinement of handling and dosing methods for rats and mice. Animal Technology and Welfare 21(2), 120-124.

Modified Handling for Mice: Handling mice by gripping the base of the tail has been shown to negatively impact animal welfare by increasing anxiety and aversion to handling. We aimed to refi ne the dosing...

Donaldson-Wing, M. 2022. Medicated jelly as a replacement for injectables and the use of Maropitant to manage itchy skin in mice. Animal Technology and Welfare 21(2), 134-136.

It is desirable to administer drugs by the least invasive route to (1) optimise welfare, (2) reduce the risk of injury to animal handlers and (3) minimise the impact of restraint and transient pain on...

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...

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...