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. 
Klune, C. B., Larkin, A. E., Leung, V. S. Y. et al. 2019. Comparing the Rat Grimace Scale and a composite behaviour score in rats. PLOS ONE 14(5), e0209467.

There is a growing interest in the use of voluntarily displayed ongoing behaviours in laboratory animals to assess the pain experience. In rats, two behavioural pain scales, the Rat Grimace Scale (RGS, a facial expression...

Améndola, L., Ratuski, A., Weary, D. M. 2019. Variation in the onset of CO2-induced anxiety in female Sprague Dawley rats. Scientific Reports 9, 19007.

Carbon dioxide (CO2) is commonly used to kill laboratory rats. Rats find CO2 aversive and aversion varies between individuals, indicating that rats vary in CO2 sensitivity. Healthy humans experience feelings of anxiety at concentrations similar...

Cox, R. J., Nol, P., Ellis, C. K. et al. 2019. Research with agricultural animals and wildlife. ILAR Journal 60(1), 66-73.

In fiscal year 2016, agricultural animals such as swine, sheep, goats, and cattle represented 10% of the 820 812 animals used in USDA-regulated research. In addition to traditional agricultural animals, research studies using captive wildlife...

Dunford, K., Hakkesteeg, J., Wilson, C. 2019. Stiff as a board: Measuring rigor mortis in zebrafish. Animal Technology and Welfare 18(3), 203-205.

Schedule one killing (S1K) methods require a two-step process: a humane method of death, typically for Zebrafish an anaesthetic overdose and confirmation of death, such as confirmation of rigor mortis. There is widespread variation of...

Thurman, C. E., Rasmussen, S., Prestia, K. A. 2019. Effect of 3 euthanasia methods on serum yield and serum cortisol concentration in zebrafish (Danio rerio). JAALAS 58(6), 823–828.

Zebrafish are an important model in neuroscience and developmental biology and are also an emerging model in hematology and immunology. Little information is available for zebrafish regarding the physiologic impact of different euthanasia methods and...

Makowska, I. J., Weary, D. M. 2019. A good life for laboratory rodents? ILAR Journal 60(3), 373-388.

Most would agree that animals in research should be spared “unnecessary” harm, pain, or distress, and there is also growing interest in providing animals with some form of environmental enrichment. But is this the standard...

Gent, T. C., Detotto, C., Vyssotski, A. L. et al. 2018. Epileptiform activity during inert gas euthanasia of mice. PLOS ONE 13(4), e0195872.

Carbon dioxide (CO2) is one of the most commonly used euthanasia agents for mice, yet it is highly aversive and nociceptive. Inert gases are a possible alternative, however there are qualitative reports of seizures resulting...

Kells, N. J., Beausoleil, N. J., Sutherland, M. A. et al. 2018. Electroencephalographic responses of anaesthetised rats to carbon dioxide inhalation. Animal Welfare 27(3), 215-223.

Exposure to high concentrations of CO2 is a common means of stunning and killing laboratory rodents. However, there is concern regarding the potential for animals to have aversive experiences, such as pain or breathlessness, prior...

Lofgren, J., Miller, A. L., Shan Lee, C. C. et al. 2018. Analgesics promote welfare and sustain tumour growth in orthotopic 4T1 and B16 mouse cancer models. Laboratory Animals 52(4), 351-364.

Murine orthotopic cancer models often require surgery, potentially causing pain or distress. However, analgesics are often withheld because they may alter tumour development. Two orthotopically implanted cancers were investigated in mice pre-treated with meloxicam (10...

Khoo, S. Y.-S., Lay, B. P. P., Joya, J. et al. 2018. Local anaesthetic refinement of pentobarbital euthanasia reduces abdominal writhing without affecting immunohistochemical endpoints in rats. Laboratory Animals 52(2), 152-162.

Sodium pentobarbital is a commonly used agent for euthanizing laboratory rats, however its high pH can cause abdominal discomfort after intraperitoneal injection. Previous studies suggest that the addition of a local anaesthetic may alleviate this...

Evangelista-Vaz, R., Bergadano, A., Arras, M. et al. 2018. Analgesic efficacy of subcutaneous–oral dosage of tramadol after surgery in C57BL/6J mice. JAALAS 57(4), 368-375.

This study investigated the analgesic activity of tramadol in female C57BL/6J mice by using a single subcutaneous injection (25 mg/kg) of tramadol combined with the same dose given in drinking water for 24 h. We...

Beninson, J. A., Lofgren, J. L., Lester, P. A. et al. 2018. Analgesic efficacy and hematologic effects of robenacoxib in mice. JAALAS 57(3), 258-267.

NSAID analgesics may confound models that require inflammation to mimic disease development in humans. This effect presents a challenge for veterinary staff and investigators, because surgery is often necessary to create mouse models of disease...

Fox, L., Mans, C. 2018. Analgesic efficacy and safety of buprenorphine in chinchillas (Chinchilla lanigera). JAALAS 57(3), 286-290.

Buprenorphine is routinely used in chinchillas at reported doses of 0.01 to 0.1 mg/kg IM or SC. However, these dose recommendations are based on anecdotal reports or extrapolation from studies in other species. Therefore, the...

Evenson, E. A., Mans, C. 2018. Analgesic efficacy and safety of hydromorphone in chinchillas (Chinchilla lanigera). JAALAS 57(3), 282-285.

Limited information is available regarding the efficacy of opioid analgesics in chinchillas. Here we sought to evaluate the analgesic efficacy and safety of hydromorphone in chinchillas. In a randomized, controlled, blind, complete crossover design, hydromorphone...

Chatigny, F., Creighton, C. M., Stevens, E. D. 2018. Updated review of fish analgesia. JAALAS 57(1), 5-12.

Analgesics are an integral part of routine pain management in mammals, yet their use in fish is still limited. Some recommendations on the use of analgesics in fish are currently in the literature; however, information...

Dudley, E. S., Boivin, G. P. 2018. Evaluation of a commercially available euthanasia solution as a voluntarily ingested euthanasia agent in laboratory mice. JAALAS 57(1), 30-34.

All currently accepted methods of euthanasia for laboratory mice involve some degree of stress, fear, anxiety, or pain. We evaluated the voluntary oral administration of a euthanasia drug in 99 male and 81 female mice...

Wallace, C. K., Bright, L. A., Marx, J. O. et al. 2018. Effectiveness of rapid cooling as a method of euthanasia for young zebrafish (Danio rerio). JAALAS 57(1), 58-63.

Despite increased use of zebrafish (Danio rerio) in biomedical research, consistent information regarding appropriate euthanasia methods, particularly for embryos, is sparse. Current literature indicates that rapid cooling is an effective method of euthanasia for adult...

Lahger, C., Laska, M. 2018. Behavioral responses of CD-1 mice to conspecific and heterospecific blood odors and to a blood odor component. Physiology & Behavior 184, 2015-210.

The odor of blood may have both aversive and attractive properties for mammals, depending on the species of the odor donor and the species perceiving the odor. To better understand the informational content of blood...

Jirkof, P., Arras, M., Cesarovic, N. 2018. Tramadol:Paracetamol in drinking water for treatment of post-surgical pain in laboratory mice. Applied Animal Behaviour Science 198, 95-100.

In the search for stress-free analgesia administration for laboratory mice suffering pain, oral delivery of Tramadol:Paracetamol (T:P) shows great promise. Here, we monitored the analgesic efficacy and side effects of a T:P combination administered solely...

Nunamaker, E. A., Goldman, J. L., Adams, C. R. et al. 2018. Evaluation of analgesic efficacy of meloxicam and 2 formulations of buprenorphine after laparotomy in female Sprague-Dawley rats. JAALAS 57(5), 498–507.

Managing postoperative pain in rodents is an important part of any animal care and use program, and identifying an optimal analgesic plan for a surgical procedure is critical to providing for animal welfare. Opioids and...

Creamer-Hente, M. A., Lao, F. K., Dragos, Z. P. et al. 2018. Sex- and strain-related differences in the stress response of mice to CO₂ euthanasia. JAALAS 57(5), 513–519.

The 2013 edition of the AVMA Guidelines for the Euthanasia of Animals recommends a 10% to 30% volume displacement rate (VDR) per minute for CO2 euthanasia of rodents. Here we sought to evaluate behavior and...

Hickman D. L. 2018. Interpreting neuroendocrine hormones, corticosterone, and blood glucose to assess the wellbeing of anesthetized rats during euthanasia. JAALAS 57(6), 725–728.

Current recommendations for assessing animal wellbeing during euthanasia suggest that measuring neuroendocrine hormones—such as ACTH, noradrenaline, and adrenaline—is preferable to measuring corticosterone and blood glucose because of the sensitivity of neuroendocrine hormones to the acute...

Hickman D. L. 2018. Home cage compared with induction chamber for euthanasia of laboratory rats. JAALAS 57(6), 729–733.

This study compared behavioral and physiologic changes in Sprague–Dawley and Brown Norway rats that were euthanized by using a 30% volume displacement rate of CO2 in either their home cage or an induction chamber; rats...

Byrd, R., Boyd, S., Buckmaster, C. 2018. Rat thunder jacket— A zen experience. Laboratory Animal Science Professional 6(3) (September), 55-57.

Germ-free rats are fairly uncommon, relative to germ-free mice, and restraining these animals safely and effectively for compound administration and blood collection can be challenging. There are many commercially available varieties of restraint devices, but...

Marquardt, N., Feja, M., Hünigen, H. et al. 2018. Euthanasia of laboratory mice: Are isoflurane and sevoflurane real alternatives to carbon dioxide? PLOS ONE 13(9), e0203793.

In the European Union (EU) millions of laboratory mice are used and killed for experimental and other scientific purposes each year. Although controversially discussed, the use of carbon dioxide (CO2) is still permitted for killing...