Boulanger Bertolus, J., Nemeth, G., Makowska, I. J. et al. 2015. Rat aversion to sevoflurane and isoflurane. Applied Animal Behaviour Science 164, 73-80.

Virtually all rodents used in research are eventually euthanized. Best practice is to anaesthetize these animals before euthanasia using a halogenated anaesthetic such as isoflurane. Exposure to isoflurane is aversive, but less so than exposure to the commonly used carbon dioxide. Sevoflurane is a newer halogenated anaesthetic that provides a smoother induction in humans, but rodent aversion to increasing concentrations of sevoflurane has yet to be investigated. The aim of this study was to compare rat aversion to isoflurane and sevoflurane using aversion-avoidance and approach-avoidance testing. In the former, rats were tested in a light/dark box and had the choice between remaining in a preferred dark chamber filling with an anaesthetic, or escaping to an aversive bright chamber. In the latter, rats had the choice between accessing a sweet food reward in a chamber filling with an anaesthetic or escaping the chamber and forgoing the reward. In the aversion-avoidance experiment, there was no difference between the two anaesthetics in the number of rats that remained in the dark chamber until they became recumbent (11 and 12 out of 17 for isoflurane and sevoflurane exposure, respectively); however, rats were only half as likely to tolerate exposure to the anaesthetics during the second exposure than during the first (P = 0.049). In the approach-avoidance experiment, there was no difference between the two anaesthetics in the number of rats that abandoned the food reward to escape exposure. During the initial exposure, 7 of 18 rats became recumbent in the lower chamber versus just 1 of 16 rats during re-exposure (P = 0.001). We conclude that rats find isoflurane and sevoflurane similarly aversive and that both agents become more aversive upon re-exposure.

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