KETAMINE ADMINISTRATION DURING WAKING INCREASES DELTA EEG INTENSITY IN RAT SLEEP
KETAMINE ADMINISTRATION DURING WAKING INCREASES DELTA EEG INTENSITY IN RAT SLEEP
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DOI：
10.1038/npp.1993.41
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发表时间：
1993-08-01
影响因子：
7.6
通讯作者：
CAMPBELL, IG
中科院分区：
文献类型：
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作者：
FEINBERG, I;CAMPBELL, IG
氯胺酮可以提高大脑边缘结构的代谢率。我们利用这一行为来验证delta睡眠稳态模型的一个假设：在随后的非快速眼动（NREM）睡眠中，可塑性神经元系统清醒代谢率的增加会增加delta脑电图（EEG）强度。在单独的实验中，我们给Sprague-Dawley大鼠腹腔注射氯胺酮15、25或50 mg/kg（0.055、0.091、0.18 mmol/kg）三次，大约每隔一小时，在黑暗（清醒）期间；最后一次给药是在轻度（睡眠）期开始前4至5小时。服用氯胺酮后，NREM持续时间和δ脑电图强度（振幅和发生率）均明显高于对照组（生理盐水注射）。这种增加的幅度使其成为迄今为止观察到的最大的药物诱导的三角洲睡眠刺激之一。由于氯胺酮在整个大脑中产生广泛的代谢变化，而且它还对几种受体起作用，对这种效应的解释变得复杂起来。然而，由于氯胺酮的主要作用是非竞争性地阻断由n -甲基- d -天冬氨酸受体控制的阳离子通道，我们的数据与最近的观察结果相结合，表明兴奋性氨基酸受体系统参与睡眠调节。
Ketamine is known to increase the metabolic rate of limbic brain structures. We exploited this action to test a hypothesis of the homeostatic model of delta sleep: that an increase in the waking metabolic rate of plastic neuronal systems would increase delta electroencephalographic (EEG) intensity in subsequent nonrapid-eye-movement (NREM) sleep. In separate experiments, we gave intraperitoneal injections of ketamine to Sprague-Dawley rats of either 15, 25, or 50 mg/kg (0.055, 0.091, 0.18 mmol/kg) three times, at approximately hourly intervals, during the dark (waking) period; the last dose was given 4 to 5 hours before onset of the light (sleep) period. After ketamine, both NREM duration and delta EEG intensity (amplitude and incidence) increased significantly over control (saline injections) levels. The magnitude of this increase places it among the largest pharmacologically induced stimulations of delta sleep yet observed. The interpretation of this effect is complicated by the fact that ketamine produces widespread metabolic changes throughout the brain and it also acts on several receptor classes. However, since ketamine's major action is noncompetitive blockade of the cation channel gated by the N-methyl-D-aspartate receptor, our data join recent observations that suggest that excitatory amino acid receptor systems are involved in sleep regulation.