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大鼠异氟烷-氧化亚氮麻醉后空间记忆任务获取的长期损害

Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats.

作者信息

Culley Deborah J, Baxter Mark G, Yukhananov Rustam, Crosby Gregory

机构信息

Department of Anesthesia, Harvard Medical School, Brigham & Women's Hospital, Boston, Massachusetts, USA.

出版信息

Anesthesiology. 2004 Feb;100(2):309-14. doi: 10.1097/00000542-200402000-00020.

DOI:10.1097/00000542-200402000-00020
PMID:14739805
Abstract

BACKGROUND

The authors demonstrated previously that isoflurane-nitrous oxide anesthesia attenuates performance improvement on an already-learned spatial memory task and that the effect persists for weeks. This experiment was designed to test the hypothesis that learning of new information is particularly susceptible to prolonged disruption after general anesthesia.

METHODS

Six- (n = 5) and 20- (n = 5) month-old male Fischer 344 rats were anesthetized for 2 h with 1.2% isoflurane, 70% nitrous oxide, and 30% oxygen. Age-matched control rats received 30% oxygen and 70% nitrogen (n = 5 per group). Rats breathed spontaneously, and anesthetic and oxygen concentrations were measured. Spatial learning was assessed daily for 21 days on a 12-arm radial maze (RAM) beginning 48 h after anesthesia. In a post hoc experiment to examine locomotion, swim speed was assessed in a separate group of identically treated rats (n = 3 per group) for 4 days beginning 48 h after anesthesia.

RESULTS

Aged rats were slower to complete the maze, made fewer correct choices before first error, and made more errors at baseline than young rats (P < 0.05). Anesthesia worsened maze performance in both age groups, as evidenced by increased time to complete the maze and a decreased number of correct choices before first error (P < 0.05), but there were no statistically significant differences in total number of errors. Interestingly, there were no age-by-anesthesia interactions. Aged rats swam slower than adult rats (P < 0.001), but there were no differences between the control and anesthesia groups.

CONCLUSIONS

Isoflurane-nitrous oxide anesthesia is associated with a persistent deficit in RAM performance that is not explained by impaired locomotion. This impairment occurs in adult and aged rats, indicating that it is not an age-specific phenomenon. Thus, RAM performance is altered after general anesthesia for longer than predicted by the pharmacology of the drugs used, which, by inference, suggests a long-term deficit in learning/memory.

摘要

背景

作者先前证明,异氟烷 - 氧化亚氮麻醉会削弱在已学会的空间记忆任务中的表现提升,且这种影响会持续数周。本实验旨在检验以下假设:新信息的学习在全身麻醉后尤其容易受到长期干扰。

方法

将6月龄(n = 5)和20月龄(n = 5)的雄性Fischer 344大鼠用1.2%异氟烷、70%氧化亚氮和30%氧气麻醉2小时。年龄匹配的对照大鼠接受30%氧气和70%氮气(每组n = 5)。大鼠自主呼吸,并测量麻醉剂和氧气浓度。在麻醉后48小时开始,在12臂放射状迷宫(RAM)上每天评估空间学习情况,持续21天。在一项事后实验中,为检查运动能力,从另一组接受相同处理的大鼠(每组n = 3)中,在麻醉后48小时开始,连续4天评估游泳速度。

结果

老年大鼠完成迷宫的速度比年轻大鼠慢,在首次犯错前做出的正确选择更少,且在基线时的错误更多(P < 0.05)。麻醉使两个年龄组的迷宫表现都变差,表现为完成迷宫的时间增加以及首次犯错前正确选择的数量减少(P < 0.05),但在错误总数上没有统计学显著差异。有趣的是,不存在年龄与麻醉的交互作用。老年大鼠游泳速度比成年大鼠慢(P < 0.001),但对照组和麻醉组之间没有差异。

结论

异氟烷 - 氧化亚氮麻醉与放射状迷宫表现的持续缺陷相关,这不能用运动能力受损来解释。这种损害在成年和老年大鼠中均会发生,表明这不是特定年龄的现象。因此,全身麻醉后放射状迷宫表现的改变比所用药物的药理学预测的时间更长,由此推断,这表明学习/记忆存在长期缺陷。

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