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. 
Weaver, H. L., Carbaugh, C. M., Madejczyk, M. S. et al. 2024. Comparison of tricaine methanesulfonate (MS-222) and alfaxalone anesthesia in zebrafish (Danio rerio). JAALAS 63(1), 74–80.

The research use of zebrafish has risen exponentially over the past decade while anesthetic options have remained largely unchanged.6 ricaine methanesulfonate (MS-222) is widely accepted as an anesthetic for routine husbandry procedures, however it has...

Maidanskaia, E. G., Mirra, A., Marchionatti, E. et al. 2023. Antinociceptive, sedative and excitatory effects of intravenous butorphanol administed alone or in combination with detomidine in calves: A prospective, randomized, blinded cross-over study. Animals 13(12), 1943.

The diagnostic and therapeutic procedures performed under sedation or general anesthesia in bovines are numerous. The analgesic drugs that can be legally used are few, making perioperative analgesia challenging. (2) Methods: Calves were administered butorphanol...

Chakravarty, S., Donoghue, J., Waite, A. S. et al. 2023. Closed-loop control of anesthetic state in nonhuman primates. PNAS Nexus 2(10), 293.

Research in human volunteers and surgical patients has shown that unconsciousness under general anesthesia can be reliably tracked using real-time electroencephalogram processing. Hence, a closed-loop anesthesia delivery (CLAD) system that maintains precisely specified levels of...

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 (

Webb, J. K., Keller, K. A., Chinnadurai, S. K. et al. 2023. Use of alfaxalone in bearded dragons (Pogona vitticeps): Optimizing pharmacodynamics and evaluating cardiogenic effects via echocardiography. Journal of the American Veterinary Medical Association 261(1), 126–131.

OBJECTIVE Bearded dragons (Pogona vitticeps), a popular zoological companion species, frequently require sedation for procedures. A novel formulation of alfaxalone with preservatives was FDA approved for 28-day use after the vial is breached. Research has...

Mainau, E., Llonch, P., Temple, D. et al. 2022. Alteration in activity patterns of cows as a result of pain due to health conditions. Animals 12(2), 176.

The main conditions and diseases considered painful in dairy cows are mastitis, lameness, calving (including dystocia and caesarean section) and metritis. The cattle literature reports that deviation from normal daily activity patterns (both increased and/or...

Leyden, C., Brüggemann, T., Debinski, F. et al. 2022. Efficacy of tricaine (MS-222) and hypothermia as anesthetic agents for blocking sensorimotor responses in larval zebrafish. Frontiers in Veterinary Science 9, 864573.

Tricaine, or MS-222, is the most commonly used chemical anesthetic in zebrafish research. It is thought to act via blocking voltage-gated sodium channels, though its mechanism of action, particularly at the neuronal level, is not...

Griffioen, A. B., Janssen, W., Menke,T. et al. 2022. Does tagging transparent fish increase predation risk? A laboratory study with glass eel (Anguilla anguilla) and sea bass (Dicentrarchus labrax). Journal of Fish Biology 100(1), 184-191.

Barriers in the estuaries of the rivers prevent the immigration of glass eels (Anguilla anguilla) arriving on the European coast every spring. This leads to an unnatural accumulation of migrating glass eels below the barriers...

Swarr, T. R., Myrick, C. A., Fitzpatrick, R. M. 2022. Tag retention in and effects of passive integrated transponder tagging on survival and swimming performance of a small-bodied darter. Journal of Fish Biology 100(3), 705-714.

Fisheries biologists have been hesitant to use passive integrated transponder (PIT) tags in small-bodied fishes (40–200 mm TL) such as darters (Percidae: Etheostomatinae) because of the fishes' size and potential effect on swimming performance. The authors used...

Buckmaster, C. L., Levesque, D., LaFollette, M. et al. 2022. Five hot topics in refinement of nonhuman primate neuroscience research. Laboratory Animal Science Professional 10(1) (January/February), 24-26.

Members of the North American 3Rs Collaborative (NA3RsC) refinement initiative have chosen to summarize developments in five hot topics of interest: 1. Tips for welfare-friendly transport, chairing, and restraint; 2. Guidance on refining food and...

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...

Paterson, E. A., Turner, P. V. 2022. Challenges with assessing and treating pain in research primates: A focused survey and literature review. Animals 12(17), 2304.

Research primates may undergo surgical procedures making effective pain management essential to ensure good animal welfare and unbiased scientific data. Adequate pain mitigation is dependent on whether veterinarians, technicians, researchers, and caregivers can recognize and...

Windsor, P. A. 2022. Role of topical anaesthesia in pain management of farm animals, a changing paradigm. Animals 12(18), 2459.

Field evidence indicates that livestock producers are motivated by access to products that readily deliver pain management during husbandry interventions and, more recently, viral epidermal infectious diseases, including FMD. There has been impressive adoption in...

Bethell, E. J., Khan, W., Hussain, A. 2022. A deep transfer learning model for head pose estimation in rhesus macaques during cognitive tasks: Towards a nonrestraint noninvasive 3Rs approach. Applied Animal Behaviour Science 255, 105708.

Head orientation is a measure of attention used in behavioral psychological research with non-human primates. It is used across a broad range of disciplines and settings, from the field to the laboratory. Field methods are...

Runde, B. J., Buckel, J. A., Bacheler, N. M. et al. 2022. Evaluation of six methods for external attachment of electronic tags to fish: Assessment of tag retention, growth and fish welfare. Journal of Fish Biology 101(3), 419-430.

External attachment of electronic tags has been increasingly used in fish studies. Many researchers have used ad hoc attachment methods and provided little or no validation for the assumption that tagging itself does not bias...

Jacob, G., Katti, H., Cherian, T. et al. 2021. A naturalistic environment to study visual cognition in unrestrained monkeys. eLife 10, e63816.

Macaque monkeys are widely used to study vision. In the traditional approach, monkeys are brought into a lab to perform visual tasks while they are restrained to obtain stable eye tracking and neural recordings. Here...

Bekkozhayeva, D., Cisar, P. 2022. Image-based automatic individual identification of fish without obvious patterns on the body (scale pattern). Applied Sciences 12(11), 5401.

The precision fish farming concept has been widely investigated in research and is highly desirable in aquaculture as it creates opportunities for precisely controlling and monitoring fish cultivation processes and increasing fish welfare. The automatic...

Mumm, L. E., Mans, C. 2022. Evaluation of dexmedetomidine-midazolam sedation in budgerigars (Melopsittacus undulatus). Journal of the American Veterinary Medical Association 260(10), 1194–1199.

OBJECTIVE To evaluate the sedative effects of IM administration of a high or low dose of dexmedetomidine in combination with midazolam in budgerigars (Melopsittacus undulatus). ANIMALS 20 healthy adult budgerigars. PROCEDURES In a prospective, randomized...

Sartini, I., Łebkowska-Wieruszewska, B., Gbylik-Sikorska, M. et al. 2022. Acetaminophen pharmacokinetics in geese. Journal of the American Veterinary Medical Association 260(12), 1–8.

OBJECTIVE To evaluate the pharmacokinetics of acetaminophen (APAP) after single-dose IV and PO in the goose; to quantify APAP and its main metabolites in goose muscle, heart, lung, liver, and kidney; and to perform a...

Owen, J. P., Kelsh, R. N. 2021. A suitable anaesthetic protocol for metamorphic zebrafish. PLOS ONE 16(3), e0246504.

Zebrafish are frequently used as a means to investigate development. These studies increasingly require repeated anaesthesia of zebrafish during juvenile (i.e. metamorphic) stages. The effects of anaesthesia during this time remain poorly studied. The aim...

Thomsen, P. T., Hansen, J. H., Herskin, M. S. 2021. Dairy calves show behavioural responses to hot iron disbudding after local anaesthesia with procaine. Veterinary Record 188(4), 270-276.

Background: The efficacy of procaine as anaesthetic for disbudding of calves is largely unknown. Likewise, information about effect of interval from local anaesthesia to disbudding and the size of the hot iron used is missing...

Sheil, M., Chambers, M., Polkinghorne, A. et al. 2021. Topical application of lidocaine and bupivacaine to disbudding wounds in dairy calves: Safety, toxicology and wound healing. Animals 11(3), 869.

Tri-Solfen® is a combination topical anaesthetic and antiseptic solution containing lidocaine, bupivacaine, adrenaline and cetrimide. Applied to wounds, it is reported to reduce the pain experienced by calves following thermocautery disbudding. While lidocaine and bupivacaine...

Rácz, A., Allan, B., Dwyer, T. et al. 2021. Identification of individual zebrafish (Danio rerio): A refined protocol for VIE tagging whilst considering animal welfare and the principles of the 3Rs. Animals 11(3), 616.

In aquatic ecology, studies have commonly employed a tagging technique known as visible implant elastomer (VIE). This method has not been widely adopted by the zebrafish research community and also lacks refinement with regard to...

Steagall, P. V., Bustamante, H., Johnson, C. B. et al. 2021. Pain management in farm animals: Focus on cattle, sheep and pigs. Animals 11(6), 1483.

Pain causes behavioral, autonomic, and neuroendocrine changes and is a common cause of animal welfare compromise in farm animals. Current societal and ethical concerns demand better agricultural practices and improved welfare for food animals. These...

Haertel, A. J., Schultz, M. A., Colgin, L. M. et al. 2021. Predictors of subcutaneous injection site reactions to sustained-release buprenorphine in rhesus macaques (Macaca mulatta). JAALAS 60(3), 329-336.

Subcutaneous injection site reactions to sustained-release buprenorphine hydrochloride (Buprenorphine SR) in macaques have been reported in only a single case report. In the current study, we evaluated the incidence rate and predictors of buprenorphine SR...