Amnesic concentrations of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, 2N) and isoflurane alter hippocampal θ oscillations in vivo
Amnesic concentrations of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, 2N) and isoflurane alter hippocampal θ oscillations in vivo
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DOI：
10.1097/01.anes.0000267600.09764.af
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发表时间：
2007-06-01
期刊：
影响因子：
8.8
通讯作者：
Pearce, Robert A.
中科院分区：
文献类型：
--
作者：
Perouansky, Misha;Hentschke, Harald;Pearce, Robert A.
背景：药物引起的暂时性遗忘是全身麻醉的主要目标之一。非固定剂1，2-二氯六氟环丁烷(F6，又称2N)在与异氟醚相似的相对浓度下，即亲脂性校正后，损害了海马依赖的学习能力。海马theta振荡在体内促进记忆过程，在体外促进突触可塑性(一种记忆的细胞模型)，被认为是一种支持记忆编码的电路水平现象。因此，作者研究了F6和F6对theta振荡(4-12 Hz)的影响。方法：将13只成年大鼠植入多道深度电极测量微脑电，并将其暴露于不同浓度的异氟烷和F6中，以产生遗忘。其中五只动物也在没有注射药物的情况下进行了对照实验。作者记录了行为状态和海马场电位。结果：异氟醚和F6的检测浓度分别为0.035%~0.77%和0.5%~3.6%。异氟醚增加了动物保持不动的时间，与镇静相一致，而F6的作用相反。当动物不动时，theta频段的脑电功率低于它们探索环境时的脑电功率。F6抑制了theta频段的振荡功率。异氟醚可在不降低theta频段总功率的情况下减缓theta振荡。结论：药物引起的theta振荡改变可能是F6和异氟醚引起的遗忘症的共同基础。不同的模式表明，这些药物通过作用于不同的分子和/或细胞靶点来改变网络活性。
Background: Drug-induced temporary amnesia is one of the principal goals of general anesthesia. The nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, also termed 2N) impairs hippocampus-dependent learning at relative, i.e., lipophilicity-corrected, concentrations similar to isoflurane. Hippocampal theta oscillations facilitate mnemonic processes in vivo and synaptic plasticity (a cellular model of memory) in vitro and are thought to represent a circuit level phenomenon that supports memory encoding. Therefore, the authors investigated the effects of F6 and isoflurane on theta oscillations (4-12 Hz).Methods: Thirteen adult rats were implanted with multichannel depth electrodes to measure the microelectroencephalogram and were exposed to a range of concentrations of isoflurane and F6 spanning the concentrations that produce amnesia. Five of these animals also underwent control experiments without drug injection. The authors recorded the behavioral state and hippocampal field potentials. They confirmed the electrode location postmortem by histology.Results: The tested concentrations for isoflurane and F6 ranged from 0.035% to 0.77% and from 0.5% to 3.6%, respectively. isoflurane increased the fraction of time that the animals remained immobile, consistent with sedation, whereas F6 had the opposite effect. Electroencephalographic power in the theta band was less when the animals were immobile than when they explored their environment. F6 suppressed the power of oscillations in the theta band. Isoflurane slowed theta oscillations without reducing total power in the theta band.Conclusions: Drug-induced changes in theta oscillations may be a common basis for amnesia produced by F6 and isoflurane. The different patterns suggest that these drugs alter network activity by acting on different molecular and/or cellular targets.