マウスにおける睡眠導入薬によるイソフルラン麻酔の延長作用に及ぼすサーカディアンリズムの影響

抄録

We previously reported that brotizolam, a benzodiazepine analog, but not suvorexant, an orexin receptor antagonist, delayed the recovery from isoflurane anesthesia in ICR mice. However, the effects of hypnotics can be affected by circadian rhythm. Using ICR mice and three inbred strains (sighted C57BL/6J and blind FVB/N and C3H/HeN mice), locomotor activity was measured during every 6 hours from zeitgeber time (ZT) 0, and the effects of brotizolam or suvorexant on isoflurane anesthesia were compared during light period and dark period. Although the locomotor activities were highest at ZT12-18 in all the strains examined, there was no significant difference between the activities at ZT0-6, ZT6-12, and ZT18-24 in the blind mice. In ICR mice, the delayed effect of brotizolam on recovery from isoflurane anesthesia in dark period was weaker than that in light period, while the delayed effect of suvorexant was observed only in dark period. In C57/BL6J mice, the delayed effect of brotizolam was remarkable, compared to other strains, and stronger in light period than in dark period, while the delayed effect of suvorexant was observed in both light and dark periods. In the blind mice, the delayed effect of brotizolam was slightly, but significant, and similar in both light and dark periods, while suvorexant did not influence the recovery from isoflurane anesthesia in both periods. These results suggested that the effects of hypnotics was affected by circadian rhythm, and that the daily light-dark stimuli may be important for the chronopharmacological effects of hypnotics.