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...

Kaiser, S., Korte, A., Wistuba, J. et al. 2023. Effects of castration and sterilization on baseline and response levels of cortisol—A case study in male guinea pigs. Frontiers in Veterinary Science 9, 1093157.

An uncontrolled reproduction of animals in human hands should be avoided. To meet this goal, animals are widely castrated, i.e., the gonads are completely removed. Since the gonads are the most important source of sex...

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...

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...

Pérez-Martín, E., Coto-Vilcapoma, A., Castilla-Silgado, J. et al. 2023. Refining stereotaxic neurosurgery techniques and welfare assessment for long-term intracerebroventricular device implantation in rodents. Animals 13(16), 2627.

Stereotaxic surgeries enable precise access to specific brain regions, being of particular interest for chronic intracerebroventricular drug delivery. However, the challenge of long-term studies at this level is to allow the implantation of drug storage...

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...

Buhr, P., Kolstrup, S., Nikolajsen, L.-L. et al. 2023. The anaesthetic effects of ketamine/xylazine/midazolam in C57Bl/6JRj mice. Scandinavian Journal of Laboratory Animal Science 49, 21–27.

We wished to improve the efficacy and safety of ketamine/xylazine anaesthesia in C57Bl/6JRj mice and achieve a surgical anaesthesia lasting 20-30 minutes, aiming at fewer anaesthesia related deaths and using the subcutaneous injection route to...

Calisir, M., Yilmaz, O., Kolatan, H. E. et al. 2023. Effects of litter size and caging on physical and mental development in rats. Physiology & Behavior 267, 114200.

As a multidisciplinary field, laboratory animal science promotes or accelerates the emergence of innovative ideas and products. As research has increased, so has the demand for laboratory animals with reliable, standardized characteristics. Thus, the breeding...

Costa, R. S., Ciotti-McClallen, M., Tilley, R. et al. 2023. Intramuscular alfaxalone with or without buprenorphine or hydromorphone provides sedation with minimal adverse effects in healthy rabbits (Oryctolagus cuniculus) in a randomized blinded controlled trial. Journal of the American Veterinary Medical Association 261(2), 223–228.

OBJECTIVE To evaluate the effects of alfaxalone administered IM with or without buprenorphine or hydromorphone in healthy rabbits (Oryctolagus cuniculus). ANIMALS 24 male rabbits undergoing elective orchiectomy between August 21, 2021, and November 6, 2021...

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...

Cho, E., Walsh, C. A., D’Angelo-Gavrish, N. M. et al. 2023. Effects of housing density on reproductive performance, intracage ammonia, and welfare of mice continuously housed as breeders in standard mouse and rat caging. JAALAS 62(2), 116–122.

Maintaining compliance with cage density recommendations in The Guide for the Care and Use of Laboratory Animals precludes continuous trio breeding in standard-sized mouse cages. This study evaluated and compared several parameters of reproductive performance...

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...

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...

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...

Xie, W., Lorenz, M., Poosch, F. et al. 2022. 3D-printed lightweight dorsal skin fold chambers from PEEK reduce chamber-related animal distress. Scientific Reports 12(1), 11599.

The dorsal skinfold chamber is one of the most important in vivo models for repetitive longitudinal assessment of microcirculation and inflammation. This study aimed to refine this model by introducing a new lightweight chamber made...

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...

Álvarez, E. R., Solé, L. V., Mateo, A. G. de C. 2022. Comparison of subcutaneous sedation with alfaxalone or alfaxalone-midazolam in pet guinea pigs (Cavia porcellus) of three different age groups. Journal of the American Veterinary Medical Association 260(9), 1024–1030.

OBJECTIVE To compare the cardiorespiratory effects, quality and duration of sedation of 2 subcutaneous sedation protocols for noninvasive procedures in guinea pigs (GPs). ANIMALS 24 pet GPs (15 females, 9 males) of 3 different age...

Huss, M. K., Pacharinsak, C. 2022. A review of long-acting parenteral analgesics for mice and rats. JAALAS 61(6), 595–602.

Appropriate analgesia is a crucial part of rodent postoperative and postprocedural pain. Providing appropriate analgesia is an ethical obligation, a regulatory requirement, and an essential element of obtaining quality scientific results and conducting reproducible data...

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...

Prior, H., Holbrook, M. 2021. Strategies to encourage the adoption of social housing during cardiovascular telemetry recordings in non-rodents. Journal of Pharmacological and Toxicological Methods 108, 106959.

The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) is working with industry to promote social housing during cardiovascular telemetry recordings within non-rodent safety pharmacology and toxicology studies. Following surveys...