Abstract
Isoflurane was previously the major clinical anesthetic agent but is now mainly used for veterinary anesthesia. Studies have reported widespread sites of action of isoflurane, suggesting a wide array of side effects besides sedation. In the present study, we phenotyped isoflurane-treated mice to investigate the postanesthetic behavioral effects of isoflurane. We applied comprehensive behavioral test batteries comprising sensory test battery, motor test battery, anxiety test battery, depression test battery, sociability test battery, attention test battery, and learning test battery, which were started 7 days after anesthesia with 1.8% isoflurane. In addition to the control group, we included a yoked control group that was exposed to the same stress of handling as the isoflurane-treated animals before being anesthetized. Our comprehensive behavioral test batteries revealed impaired latent inhibition in the isoflurane-treated group, but the concentration of residual isoflurane in the brain was presumably negligible. The yoked control group and isoflurane-treated group exhibited higher anxiety in the elevated plus-maze test and impaired learning function in the cued fear conditioning test. No influences were observed in sensory functions, motor functions, antidepressant behaviors, and social behaviors. A number of papers have reported an effect of isoflurane on animal behaviors, but no systematic investigation has been performed. To the best of our knowledge, this study is the first to systematically investigate the general health, neurological reflexes, sensory functions, motor functions, and higher behavioral functions of mice exposed to isoflurane as adults. Our results suggest that the postanesthetic effect of isoflurane causes attention deficit in mice. Therefore, isoflurane must be used with great care in the clinical setting and veterinary anesthesia.
Highlights
At one time, the halogenated ether isoflurane was the major anesthetic agent in clinical settings, but it is mainly used for veterinary anesthesia
Our results indicate that the anesthesia changes neural plasticity, and that isoflurane-treated animals may be susceptible to external inputs for several days after administration of the anesthetic
Mice exposed to 1.8% isoflurane for 2 h, which is equivalent to normal surgical concentrations, exhibited impaired latent inhibition 7 days after anesthesia, even though the concentrations of residual isoflurane in the brain was presumably negligible at this time
Summary
The halogenated ether isoflurane was the major anesthetic agent in clinical settings, but it is mainly used for veterinary anesthesia. Previous studies reported that isoflurane induces sedation by modifying the GABAA receptor, two-pore potassium channel, glycine receptor, 5-HT3 receptor, kainate receptor, NMDA receptor, voltage-gated potassium channel, and nicotinic/muscarinic acetylcholine receptor [1,2,3,4,5]. Our results indicate that the anesthesia changes neural plasticity, and that isoflurane-treated animals may be susceptible to external inputs for several days after administration of the anesthetic. These findings suggest that animals exposed to anesthetics may exhibit multiple potential effects on a variety of behaviors several days after exposure. Because the results of behavioral studies are not always consistent among research labs [10], a systematic comprehensive behavioral study of isoflurane-treated animals is needed
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