Laboratory animals are anaesthetised to avoid pain during invasive procedures. Anaesthesia is necessary for the welfare of these animals, but it is not always without problems: substandard anaesthesia can cause suffering, distort experiment results and force researchers to repeat tests on more animals.
A research group at the University of Helsinki’s Faculty of Veterinary Medicine is looking to solve these problems.
No more bulging eyes
One of the most striking problems is that certain commonly used sedatives cause exophthalmos in rats, which means their eyes bulge out of their sockets. Although this adverse effect has been known since the 1980s, the sedatives causing it remain widely used. Abnormally protruding eyes are exposed to painful injuries.
Minna Mustikka is a specialist in veterinary ophthalmology, or animal eye diseases, and now investigates in her doctoral thesis whether a drug called vatinoxan could help. A vatinoxan product originally designed for canine sedation collaboratively by the research group and the Finnish company Vetcare appears to also improve the safety of small rodents under anaesthesia.
“Vatinoxan is proving to be the genuine article: we have demonstrated that in rats, it prevents the dramatic bulging of eyes associated with the use of common sedative combinations as well as alleviating other adverse effects occurring inside the eye. The findings have already been groundbreaking for the welfare of laboratory rats,” Mustikka says.
Mustikka’s first article for her doctoral thesis has been published in the Journal of Ocular Pharmacology and Therapeutics.
More balanced vital functions
In another doctoral thesis, Emily Lindh investigates what vatinoxan does to murine blood circulation during sedation. Lindh, who is interested in laboratory animal medicine, has conducted comprehensive pioneering work on the general properties of vatinoxan as part of anaesthesia in rats and mice.
“Sedation and anaesthesia are necessary for the humane treatment of animals, but the adverse effects of the drugs used should not compromise the reliability of research findings. In my doctoral thesis, I demonstrate that vatinoxan improves tissue oxygenation in rats by reducing the adverse circulatory effects of sedatives,” Lindh says.
Lindh has shown that vatinoxan also inhibits the increase in blood glucose caused by these sedatives as well as excessive urine output in rats.
“The main goal of my doctoral research is to improve research methods in accordance with the 3R principles. Rats are still one of the most widely used species in biomedical research,” she adds.
The 3R principles guide research involving laboratory animals globally, referring to the Reduction of the number of animals used, the Replacement of animal testing with other methods whenever possible, and Refinement through which the harm caused to animals is minimised.
Animals get used to handling
Veterinarians Anna Meller and Karoliina Alm from the Laboratory Animal Centre have contributed to the studies from the beginning. They think it also matters how animals are treated before any experiments.
“These studies have confirmed the notion that rats and mice soon get used to handling by humans when it is competent and on the animal’s terms. This area should be further developed in laboratory veterinary medicine, as it would improve the reliability of research findings alongside animal welfare,” Alm says.
Drug effects are species-dependent
The research group is headed by Associate Professor of Veterinary Pharmacology Jussi Honkavaara, who has more than 20 years of experience with vatinoxan. He points out that differences between animal species stand out in anaesthesia.
“The same pharmaceutical agent can primarily boost circulation in dogs, alleviate constipation in horses and, in rodents, prevent the bulging of the eyes out of the sockets. Evolution has shaped the physiology of each species so uniquely that it is hardly worth trying to predict how new drugs could affect individual species. The answers will eventually be uncovered through high-quality basic research,” Honkavaara says.
Senior University Lecturer Marja Raekallio, who has also been involved in vatinoxan research from the beginning, considers the findings made in rodents particularly unambiguous.
“Vatinoxan has taught us a great deal about the behaviour of pharmaceutical agents in various animal species. Even though the mechanisms of action are essentially the same in mice and horses, the drug effects are emphasised in different ways. It was gratifying to see the inhibition of eye problems so evident among rodents,” Raekallio says.
Next up: mice
Next, the research will be expanded from rats to mice. In their doctoral research projects launched in early 2026, veterinarians Ilbagizadeh ”Sima” Mohabadi and Oona Miuku have already noticed that the benefits seen in rats are replicable in mice, too. However, the optimal doses differ markedly between the species.
“For us, this is above all about animal welfare, whether pets or laboratory animals. Preventing the adverse effects of anaesthesia in laboratory experiments reduces the variety in outcomes and reduces the number of rats and mice needed in the studies. In Western countries alone, a reduction of less than 1% would amount to more than a million animals spared each year. While questions remain to be answered, the impact of our researchers’ observations may become significant on a global scale,” Honkavaara notes.