Aversion to Desflurane and Isoflurane in Sprague-Dawley Rats (Rattus norvegicus)

SIMPLE SUMMARY: Euthanasia is one of the most commonly performed procedures in laboratory rodents, as the majority of animals are killed upon project completion or when humane endpoints have been reached. Overdose with carbon dioxide gas remains a widely used killing method, despite evidence it is aversive to rodents. The inhalant anesthetic isoflurane is a refinement to overdose with carbon dioxide, but also elicits aversion in rodents. The inhalant anesthetic desflurane has a faster onset of action than isoflurane and may therefore offer further refinement. In this study, rat aversion to desflurane and isoflurane was compared. Isoflurane and desflurane were similarly aversive; however, desflurane exposure resulted in a shorter time to achieve recumbency, shortening any period of potential distress. Therefore, desflurane represents a refinement over the use of isoflurane. ABSTRACT: Carbon dioxide and isoflurane are widely used for killing rats, yet may not truly achieve “euthanasia”, because they elicit aversion. The inhalant anesthetic desflurane is faster acting than isoflurane, representing a potential refinement. Using an aversion-avoidance paradigm, 24 rats were exposed to isoflurane or desflurane (n = 12 per group) at initial exposure. Fourteen rats were then re-exposed to isoflurane or desflurane (n = 7 per group), after a 7 days washout period. Initial exposure: time to recumbency was faster for desflurane than isoflurane (p = 0.0008, 95% CI [-12.9 to 32.6 s]), with 9/12 and 6/12 rats becoming recumbent, respectively. At initial exposure, there was no difference between groups in time to withdrawal (p = 0.714). At re-exposure, all rats withdrew and no rats became recumbent. Time to withdrawal at re-exposure did not differ between treatment groups (p = 0.083). Compared to initial exposure, time to withdrawal during re-exposure was similar for isoflurane (p = 0.228) and faster with desflurane (p = 0.012, 95% CI [19.1 to 49.5 s]). Isoflurane and desflurane are similarly aversive, with aversion increasing at re-exposure. The shorter time from exposure to recumbency with desflurane indicates that any distress is of a shorter duration when compared with isoflurane.