Dextroamphetamine (but Not Atomoxetine) Induces Reanimation from General Anesthesia: Implications for the Roles of Dopamine and Norepinephrine in Active Emergence.
Dextroamphetamine (but Not Atomoxetine) Induces Reanimation from General Anesthesia: Implications for the Roles of Dopamine and Norepinephrine in Active Emergence.
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DOI：
10.1371/journal.pone.0131914
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Solt K
中科院分区：
文献类型：
--
作者：
Kenny JD;Taylor NE;Brown EN;Solt K
哌甲酯可诱导啮齿动物从全身麻醉中苏醒（主动苏醒），最近的证据表明多巴胺能神经传递在产生这种效果中起重要作用。右旋安非他明引起多巴胺和去甲肾上腺素的直接释放，而托莫西汀是去甲肾上腺素的选择性再摄取抑制剂。和哌醋甲酯一样，这两种药物都是用来治疗注意力缺陷多动障碍的。在这项研究中，我们测试了右旋安非他明和阿托西汀对大鼠全身麻醉苏醒的作用。全麻苏醒的定义是矫直恢复。在连续七氟醚麻醉过程中，右旋安非他明剂量依赖性诱导行为唤醒和恢复扶正，但托莫西汀没有（各n = 6）。在相同条件下，D1多巴胺受体拮抗剂SCH-23390在右旋安非他明之前使用，翻正未恢复（n = 6）。异丙酚单次给药（8 mg/kg IV）后，生理盐水（对照品）和右旋安非他明（1 mg/kg IV）组大鼠平均苏醒时间分别为641秒和404秒（n = 8）。差异有统计学意义。虽然托莫西汀将平均急诊时间减少到566秒（n = 8），但这种减少没有统计学意义。脑电图记录的频谱分析显示，右安非他明和托莫西汀在连续七氟醚全身麻醉时均诱导峰功率从δ (0.1-4 Hz)向θ (4-8 Hz)转变，而预先给施-23390时未观察到这一现象。综上所述，右旋安非他明在啮齿类动物全身麻醉后诱导苏醒，但在相同的实验条件下，托莫西汀不会诱导唤醒反应。这支持了在全身麻醉时多巴胺能刺激产生强烈的行为唤醒反应的假设。相比之下，选择性去甲肾上腺素能刺激引起显著的神经生理变化，但不促进全麻时的行为唤醒。我们假设右旋安非他明比阿托西汀更有可能在临床上用于恢复麻醉患者的意识，主要是由于其刺激多巴胺能神经传递。
Methylphenidate induces reanimation (active emergence) from general anesthesia in rodents, and recent evidence suggests that dopaminergic neurotransmission is important in producing this effect. Dextroamphetamine causes the direct release of dopamine and norepinephrine, whereas atomoxetine is a selective reuptake inhibitor for norepinephrine. Like methylphenidate, both drugs are prescribed to treat Attention Deficit Hyperactivity Disorder. In this study, we tested the efficacy of dextroamphetamine and atomoxetine for inducing reanimation from general anesthesia in rats. Emergence from general anesthesia was defined by return of righting. During continuous sevoflurane anesthesia, dextroamphetamine dose-dependently induced behavioral arousal and restored righting, but atomoxetine did not (n = 6 each). When the D1 dopamine receptor antagonist SCH-23390 was administered prior to dextroamphetamine under the same conditions, righting was not restored (n = 6). After a single dose of propofol (8 mg/kg IV), the mean emergence times for rats that received normal saline (vehicle) and dextroamphetamine (1 mg/kg IV) were 641 sec and 404 sec, respectively (n = 8 each). The difference was statistically significant. Although atomoxetine reduced mean emergence time to 566 sec (n = 8), this decrease was not statistically significant. Spectral analysis of electroencephalogram recordings revealed that dextroamphetamine and atomoxetine both induced a shift in peak power from δ (0.1–4 Hz) to θ (4–8 Hz) during continuous sevoflurane general anesthesia, which was not observed when animals were pre-treated with SCH-23390. In summary, dextroamphetamine induces reanimation from general anesthesia in rodents, but atomoxetine does not induce an arousal response under the same experimental conditions. This supports the hypothesis that dopaminergic stimulation during general anesthesia produces a robust behavioral arousal response. In contrast, selective noradrenergic stimulation causes significant neurophysiological changes, but does not promote behavioral arousal during general anesthesia. We hypothesize that dextroamphetamine is more likely than atomoxetine to be clinically useful for restoring consciousness in anesthetized patients, mainly due to its stimulation of dopaminergic neurotransmission.
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DOI：
10.1056/nejmra0808281
发表时间：
2010-12-30
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brown EN;Lydic R;Schiff ND
通讯作者：
Schiff ND
影响因子：
9.8
作者：
Lepouse, C.;Lautner, C. A.;Leon, A.
通讯作者：
Leon, A.
影响因子：
8.8
作者：
Luo, Tao;Leung, L. Stan
通讯作者：
Leung, L. Stan
影响因子：
1.7
作者：
Chambers, Neil A.;Pascoe, Elaine;Forsyth, Ian
通讯作者：
Forsyth, Ian
DOI：
10.1073/pnas.0707146105
发表时间：
2008-01-29
影响因子：
11.1
作者：
Kelz, Max B.;Sun, Yi;Yanagisawa, Masashi
通讯作者：
Yanagisawa, Masashi