Early exposure to general anesthesia impairs social and emotional development in rats
Early exposure to general anesthesia impairs social and emotional development in rats
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DOI：
10.1007/s12035-019-01755-x
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发表时间：
2020-01-01
影响因子：
5.1
通讯作者：
Jevtovic-Todorovic, Vesna
中科院分区：
文献类型：
--
作者：
Diana, Paolo;Joksimovic, Srdjan M.;Jevtovic-Todorovic, Vesna
一些动物和新兴的人类研究表明，早期暴露于全身麻醉（GA）与复杂的社会和情感行为（如注意力不集中，冲动，焦虑倾向）以及难以进行适当的社交之间存在关联，注意力缺陷和多动型行为显着增加。为了进一步研究这些行为，并检查目前可用的啮齿动物行为模型的潜力，以指导未来评估人类的长期社会情绪障碍，我们研究了GA对焦虑/恐惧和社会行为的长期影响。我们将处于突触发生高峰期的雄性和雌性Sprague-Dawley幼年大鼠暴露于含GA的咪达唑仑（9 mg/kg，腹膜内），70%一氧化二氮（N2 O）和0.75%异氟烷（Iso）溶于29-30%氧气（实验）或空气（含30%氧气）加溶剂0.1%二甲基亚砜（Sham）中给药6 h。在青春期（旷场测试）和青年期（旷场测试，高架十字迷宫和社会新奇测试）进行行为实验。我们报告说，早期暴露于GA在大脑发育的关键阶段的结果在长期持续增加的冒险倾向和显着变化的焦虑相关的行为时，在年轻的成年大鼠进行测试。此外，我们注意到，随着社会歧视的变化，寻求新奇的倾向/不那么谨慎的行为。我们的结论是，早期暴露于麻醉可能会对情绪和社会发展产生持久的影响。重要的是，我们的研究结果表明，目前使用的啮齿动物行为模型可能是一个很好的相关性，以评估长期的社会情绪GA诱导的损害在人类中观察到的。
Several animal and emerging human studies suggest an association between an early exposure to general anesthesia (GA) and long-lasting problems with complex social and emotional behaviors such as inattentiveness, impulsivity, anxiogenic tendencies, as well as difficulties engaging in proper social intercourse, with significant increase in attention deficit and hyperactivity-type behaviors. To further investigate these behaviors, and to examine the potential of presently available rodent behavioral models to guide future assessments of long-term socio-emotional impairments in humans, we examined the long-term effects of GA on anxiety/fear and social behaviors. We exposed male and female Sprague-Dawley infant rats at the peak of their synaptogenesis to either GA containing midazolam (9 mg/kg, i.p.), 70% nitrous oxide (N2O) and 0.75% isoflurane (Iso) administered in 29-30% oxygen (experimental), or air (with 30% oxygen) plus the vehicle, 0.1% dimethyl sulfoxide (Sham) for 6 h. Behavioral experiments were conducted at adolescence (the open-field test) and young adulthood (the open-field test, the elevated plus-maze and the social novelty test). We report that an early exposure to GA during critical stages of brain development results in long-lasting increase in risk-taking tendencies and significant changes in the anxiety-related behaviors when tested in young adult rats. In addition, we noted novelty-seeking tendencies/less guarded behavior with changes in social discrimination. We conclude that early exposure to anesthesia may have lasting influences on emotional and social development. Importantly, our results show that currently used rodent behavioral models could be a good correlate to assess long-term socio-emotional GA-induced impairments observed in humans.