氟烷诱导的催眠在啮齿动物中并不伴随着食欲肽能输出的失活。
Halothane-induced hypnosis is not accompanied by inactivation of orexinergic output in rodents.
作者信息
Gompf Heinrich, Chen Jingqiu, Sun Yi, Yanagisawa Masashi, Aston-Jones Gary, Kelz Max B
机构信息
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard University Medical School, Boston, Massachusetts, USA.
出版信息
Anesthesiology. 2009 Nov;111(5):1001-9. doi: 10.1097/ALN.0b013e3181b764b3.
BACKGROUND
One underexploited property of anesthetics is their ability to probe neuronal regulation of arousal. At appropriate doses, anesthetics reversibly obtund conscious perception. However, individual anesthetic agents may accomplish this by altering the function of distinct neuronal populations. Previously the authors showed that isoflurane and sevoflurane inhibit orexinergic neurons, delaying reintegration of sensory perception as denoted by emergence. Here the authors study the effects of halothane. As a halogenated alkane, halothane differs structurally, has a nonoverlapping series of molecular binding partners, and differentially modulates electrophysiologic properties of several ion channels when compared with its halogenated ether relatives.
METHODS
c-Fos immunohistochemistry and in vivo electrophysiology were used to assess neuronal activity. Anesthetic induction and emergence were determined behaviorally in narcoleptic orexin/ataxin-3 mice and control siblings exposed to halothane.
RESULTS
Halothane-induced hypnosis occurred despite lack of inhibition of orexinergic neurons in mice. In rats, extracellular single-unit recordings within the locus coeruleus showed significantly greater activity during halothane than during a comparable dose of isoflurane. Microinjection of the orexin-1 receptor antagonist SB-334867-A during the active period slowed firing rates of locus coeruleus neurons in halothane-anesthetized rats, but had no effect on isoflurane-anesthetized rats. Surprisingly, orexin/ataxin-3 transgenic mice, which develop narcolepsy with cataplexy because of loss of orexinergic neurons, did not show delayed emergence from halothane.
CONCLUSION
Coordinated inhibition of hypothalamic orexinergic and locus coeruleus noradrenergic neurons is not required for anesthetic induction. Normal emergence from halothane-induced hypnosis in orexin-deficient mice suggests that additional wake-promoting systems likely remain active during general anesthesia produced by halothane.
背景
麻醉剂一个未被充分利用的特性是它们能够探究神经元对觉醒的调节。在适当剂量下，麻醉剂可逆性地抑制意识感知。然而，不同的麻醉剂可能通过改变不同神经元群体的功能来实现这一点。此前，作者表明异氟烷和七氟烷会抑制食欲素能神经元，延迟如苏醒所表示的感觉感知的重新整合。在此，作者研究了氟烷的作用。作为一种卤代烷烃，氟烷在结构上有所不同，具有一系列不重叠的分子结合伙伴，并且与其卤代醚类亲属相比，对几种离子通道的电生理特性有不同的调节作用。
方法
采用c-Fos免疫组织化学和体内电生理学方法评估神经元活动。在暴露于氟烷的发作性睡病食欲素/共济失调蛋白3小鼠和对照同胞中，通过行为学方法确定麻醉诱导和苏醒情况。
结果
尽管小鼠中的食欲素能神经元未受到抑制，但仍出现了氟烷诱导的催眠作用。在大鼠中，蓝斑核内的细胞外单单位记录显示，与同等剂量的异氟烷相比，氟烷给药期间的活动明显更强。在活跃期微量注射食欲素-1受体拮抗剂SB-334867-A可减缓氟烷麻醉大鼠蓝斑核神经元的放电频率，但对异氟烷麻醉大鼠没有影响。令人惊讶的是，由于食欲素能神经元缺失而患发作性睡病伴猝倒的食欲素/共济失调蛋白3转基因小鼠，并未表现出氟烷诱导的苏醒延迟。
结论
麻醉诱导并不需要对下丘脑食欲素能神经元和蓝斑核去甲肾上腺素能神经元进行协同抑制。食欲素缺乏小鼠能从氟烷诱导的催眠状态中正常苏醒，这表明在氟烷产生的全身麻醉期间，可能还有其他促进觉醒的系统保持活跃。
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