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. 2020 May 30;10(6):950.
doi: 10.3390/ani10060950.

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

Katrina Frost  1 , Maaria Shah  2 , Vivian S Y Leung  3 , Daniel S J Pang  1   3
Affiliations

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

Katrina Frost et al. Animals (Basel). .

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.

Keywords: animal welfare; aversion; aversion-avoidance; desflurane; euthanasia; isoflurane; rats; refinement.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Illustration of the aversion-avoidance testing apparatus.
Figure 2
Figure 2
Time to recumbency. During initial exposure, 9/12 and 6/12 rats became recumbent after exposure to desflurane and isoflurane, respectively. Time to recumbency was shorter in rats exposed to desflurane than isoflurane. *** p < 0.001. Data are median (middle line in box), IQR (box limits) and 10–90 percentile (whiskers).
Figure 3
Figure 3
Time to withdrawal was similar for desflurane and isoflurane during both initial and re-exposure. Times to withdrawal between initial and re-exposure was not significant for isoflurane, but was significant for desflurane (p < 0.05). Data are presented as median (middle line in box), IQR (box limits) and 10–90 percentile (whiskers). * p < 0.05.
Figure 4
Figure 4
Time to withdrawal pooled by timepoint (initial and re-exposure). Rats withdrew faster upon re-exposure (p < 0.01). Sample sizes reflect animals that withdrew. ** p < 0.01. Data are presented as median (middle line in box), IQR (box limits) and 10–90 percentile (whiskers). Solid circles indicate outliers (values lying ± 1.5 × IQR).
Figure 5
Figure 5
Total dwelling time in dark chamber (site of anesthetic gas exposure) was longer during initial exposure to both desflurane (p < 0.01) and isoflurane (p < 0.05). During initial exposure and re-exposure, dwelling time was similar between anesthetics (p > 0.05). Data are presented as median (middle line in box), IQR (box limits) and 10–90 percentile (whiskers). Horizontal dotted line indicates the maximum duration of testing (3 min). * p < 0.05, ** p < 0.01. Solid circles indicate outliers (values lying ± 1.5 × IQR).
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