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. 
Farag, A., Mandour, A. S., Hendawy, H. et al. 2023. A review on experimental surgical models and anesthetic protocols of heart failure in rats. Frontiers in Veterinary Science 10, 1103229.

Heart failure (HF) is a serious health and economic burden worldwide, and its prevalence is continuously increasing. Current medications effectively moderate the progression of symptoms, and there is a need for novel preventative and reparative...

Mauthe von Degerfeld, M., Serpieri, M., Bonaffini, G. et al. 2023. Intranasal atomization of ketamine, medetomidine and butorphanol in pet rabbits using a mucosal atomization device. Animals 13(13), 2076.

A non-invasive method of drug delivery, intranasal atomization, has shown positive results in human medicine and in some animal species. The objective of this study was to evaluate the effects of intranasal atomization, compared to...

Lupfer, G., Brandenburger, A., Machado, M. et al. 2023. Ultrasonic vocalizations near 30 kHz may indicate excitement rather than distress in female Wistar rats. Applied Animal Behaviour Science 261, 105881.

Rats emit ultrasonic vocalizations (USVs), sometimes referred to as 50-kHz vocalizations, during activities such as play and lower-frequency USVs, sometimes referred to as 22-kHz vocalizations, when experiencing distress. Definitions of 22-kHz vocalizations vary in terms...

Broadfoot, C. K., Lenell, C., Kelm-Nelson, C. A. et al. 2023. Effects of social isolation on 50-kHz ultrasonic vocalizations, affective state, cognition, and neurotransmitter concentrations in the ventral tegmental and locus coeruleus of adult rats. Behavioural Brain Research 437, 114157.

Vocal communication, cognition, and affective state are key features of sustained health and wellness, and because vocalizations are often socially-motivated, social experience likely plays a role in these behaviors. The monoaminergic systems of the ventral...

Esparza, K. 2023, August. Moving away from soiled bedding sentinels—The (R)evolution in rodent health screening. Animal Technology and Welfare 22(2), 158–160.

Traditional health monitoring methods consisted of Soiled Bedding Sentinels (SBS (i.e. animals exposed to dirty bedding from colony animals)), which require the euthanasia of SBS. Numerous studies have demonstrated that SBS may not accurately represent...

Imboden, T. J., Pownall, W. R., Rubin, S. et al. 2023. Determination of a safe sedative combination of dexmedetomidine, ketamine and butorphanol for minor procedures in dogs by use of a stepwise optimization method. Acta Veterinaria Scandinavica 65(1), 41.

In veterinary practice, most minor procedures such as radiographs, skin biopsies, and wound treatments require sedation. The combination of butorphanol, ketamine, and dexmedetomidine is commonly used, but the ideal dosages for this combination have not...

Marin, N., Moragon, A., Gil, D. et al. 2023. Acclimation and blood sampling: Effects on stress markers in C57Bl/6J mice. Animals 13(18), 2816.

Blood sampling in rodents is common practice in scientific studies. Some of the refined methods widely used are the puncture of the saphenous vein or tail vein, or even tail docking. The handling needs of...

Menard, J., Bagheri, S., Menon, S. et al. 2023. Noninvasive sampling of the small intestinal chyme for microbiome, metabolome and antimicrobial resistance genes in dogs, a proof of concept. Animal Microbiome 5(1), 64.

Background The gastrointestinal microbiome and metabolome vary greatly throughout the different segments of the gastrointestinal tract, however current knowledge of gastrointestinal microbiome and metabolome in health and disease is limited to fecal samples due to...

Ahrens Kress, A. P., Zhang, Y., Kaiser-Vry, A. R. et al. 2022. A Comparison of blood collection techniques in mice and their effects on welfare. JAALAS 61(3), 287-295.

Multiple methods are used to collect blood from mice; these methods have different effects on animal welfare. This study compared blood collection from facial, chin, and saphenous locations with regard to various parameters, including the...

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...

Scariot, P. P., Gobatto, C. A., Polisel, E. E. et al. 2022. Early-life mice housed in standard stocking density reduce the spontaneous physical activity and increase visceral fat deposition before reaching adulthood. Laboratory Animals 56(4), 344-355.

Laboratory rodents spend the entire day housed in standard cages that provide a restricted area for movements and might, therefore, limit physical activity. However, it has not been tested in immature rodents of ages ranging...

Tivey, E. K. L., Martin, J. E., Brown, S. M. et al. 2022. Sex differences in 50 kHz call subtypes emitted during tickling-induced playful behaviour in rats. Scientific Reports 12(1), 15323.

‘Tickling’ induces positive affective states in laboratory rats as evidenced by the production of 50-kHz ultrasonic vocalisations (USVs), although this has mostly been investigated in males. Juvenile rats emit distinctive 50-kHz USV subtypes. Frequency-modulated (FM)...

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...

Lima, A. F., Lima, S. G. C., Nogueira-Filho, S. L. G. et al. 2022. Vocal expression of emotions in farmed spotted paca (Cuniculus paca). Applied Animal Behaviour Science 256, 105753.

Vocal emissions in non-human mammals can be used as non-invasive indicators of animal emotion and welfare. Therefore, we aimed to validate the use of acoustic parameters as indicators of affective states and welfare in farmed...

Giral, M., Armengol, C., Gavaldà, A. 2022. Physiologic effects of housing rats in metabolic cages. Comparative Medicine 72(5), 298–305.

Currently, metabolic cages (MC) are the only way to achieve serial sampling of urine and feces in rodents. However, the use of this caging creates a dramatic change from an animal’s usual microenvironment. Here we...

Marx, A., Lenkei, R., Pérez Fraga, P. et al. 2021. Occurrences of non-linear phenomena and vocal harshness in dog whines as indicators of stress and ageing. Scientific Reports 11(1), 4468.

During social interactions, acoustic parameters of tetrapods’ vocalisations reflect the emotional state of the caller. Higher levels of spectral noise and the occurrence of irregularities (non-linear phenomena NLP) might be negative arousal indicators in alarm...

Seidisarouei, M., van Gurp, S., Pranic, N. M. et al. 2021. Distinct profiles of 50 kHz vocalizations differentiate between social versus non-social reward approach and consumption. Frontiers in Behavioral Neuroscience 15, 693698.

Social animals tend to possess an elaborate vocal communication repertoire, and rats are no exception. Rats utilize ultrasonic vocalizations (USVs) to communicate information about a wide range of socially relevant cues, as well as information...

Navarro, K. L., Huss, M., Smith, J. C. et al. 2021. Mouse anesthesia: The art and science. ILAR Journal 62(1-2), 238-273.

There is an art and science to performing mouse anesthesia, which is a significant component to animal research. Frequently, anesthesia is one vital step of many over the course of a research project spanning weeks...

Koshman, Y. E., Wilsey, A. S., Bird, B. M. et al. 2021. Automated blood sampling in canine telemetry studies: Enabling enhanced assessments of cardiovascular liabilities and safety margins. Journal of Pharmacological and Toxicological Methods 109, 107066.

Introduction: A successful integration of automated blood sampling (ABS) into the telemetry instrumented canine cardiovascular model is presented in this study. This combined model provides an efficient means to quickly gain understanding of potential effects...

Blevins, C. E., Celeste, N. A., Marx, J. O. 2021. Effects of oxygen supplementation on injectable and inhalant anesthesia in C57BL/6 mice. JAALAS 60(3), 289-297.

Oxygen supplementation is rarely considered when anesthetizing laboratory mice, despite reports that mice become profoundly hypoxic under anesthesia. Little is known about the effects of hypoxia on anesthetic performance. This article focuses on the effects...

Prior, H., Blunt, H., Crossman, L. et al. 2021. Refining procedures within regulatory toxicology studies: Improving animal welfare and data. Animals 11(11), 3057.

During the development of potential new medicines or agrochemicals, an assessment of the safety profile to humans and environmental species is conducted using a range of different in silico and in vitro techniques in conjunction...

da Silva Medeiros Elidio, H., Coelho, J. W. R., Cavalcanti Pereira da Silva, L. C. et al. 2021. Housing density and aggression in Syrian hamsters. JAALAS 60(5), 506-509.

The Syrian hamster (Mesocricetus auratus) is a solitary and naturally territorial animal, with female hamsters being more aggressive than males. This behavior makes handling difficult because they are usually housed in groups, which can lead...

Botman, J., Hontoir, F., Gustin, P. et al. 2020. Postanaesthetic effects of ketamine–midazolam and ketamine–medetomidine on gastrointestinal transit time in rabbits anaesthetised with isoflurane. Veterinary Record 186(8), 249.

Gastrointestinal stasis is a common perianaesthetic complication in rabbits. The objective of this study was to assess the impact on gastrointestinal transit time of ketamine–midazolam (KMZ) versus ketamine–medetomidine (later antagonised by atipamezole) (KMT-A) in rabbits...

Filliettaz, C., Maxwell, L., Dragon, M. et al. 2020. Novel bleeding techniques in hamsters. Laboratory Animal Science Professional 8(1) (January/February), 44-46.

Hamsters have historically been used in our pharmacokinetic (PK) studies using the retro-orbital (RO) bleeding technique to collect blood samples. If performed incorrectly, this technique has the potential for animal welfare complications not usually seen...

Nøgaard, S. A., Sand, F. W., Sørensen, D. B. et al. 2020. Four- and six-hour urinary albumin excretion is a valuable alternative to 24-h urinary albumin excretion in male db/db mice. Animal Welfare 29(2), 143-149.

In mouse (Mus musculus) models of diabetic nephropathy (DN), one of the most important read-outs is the 24-h urinary albumin excretion (UAE). The 24-h urine collection is usually performed by single housing mice in metabolic...