Stone W S, Walker D L, Gold P E
Department of Psychology, University of Virginia, Charlottesville 22903.
Physiol Behav. 1992 Sep;52(3):609-12. doi: 10.1016/0031-9384(92)90355-6.
N-Methyl-D-aspartate (NMDA) receptor blockade disrupts a variety of functions associated with neural plasticity, including acquisition of learned responses and long-term potentiation. Deficits in memory are significantly correlated with deficits in measures of paradoxical sleep in several amnesic populations. The present experiment therefore assessed whether NPC 12626, a competitive NMDA receptor antagonist, also disrupts sleep. NPC 12626 (1, 10, 50, and 100 mg/kg) or saline was administered to Sprague-Dawley rats 30 min prior to 3-h daytime recording periods. Paradoxical sleep was selectively impaired at all but the highest dose, which prevented all sleep during the recording period. Some deficits in nonparadoxical sleep first appeared at the 10 mg/kg dose but did not became prominent until the 50 mg/kg dose. The results thus show that NPC 12626 impairs sleep states in rats and demonstrate that paradoxical sleep is particularly susceptible to the effects of NMDA receptor blockade. These findings, along with previous evidence that NMDA antagonists impair waking measures of arousal, provide evidence that all sleep-wake states are impaired by NMDA receptor blockade. More generally, the results suggest that some brain mechanisms underlying sleep and memory may share common elements.
N-甲基-D-天冬氨酸（NMDA）受体阻断会破坏与神经可塑性相关的多种功能，包括习得反应的获得和长时程增强。在几个失忆群体中，记忆缺陷与异相睡眠指标的缺陷显著相关。因此，本实验评估了竞争性NMDA受体拮抗剂NPC 12626是否也会干扰睡眠。在3小时的白天记录期前30分钟，给斯普拉格-道利大鼠注射NPC 12626（1、10、50和100毫克/千克）或生理盐水。除最高剂量外，所有剂量的NPC 12626均选择性地损害异相睡眠，最高剂量在记录期内阻止了所有睡眠。非异相睡眠的一些缺陷在10毫克/千克剂量时首次出现，但直到50毫克/千克剂量时才变得明显。结果表明，NPC 12626会损害大鼠的睡眠状态，并表明异相睡眠对NMDA受体阻断的影响尤为敏感。这些发现，连同之前NMDA拮抗剂损害觉醒唤醒指标的证据，证明了所有睡眠-觉醒状态都会受到NMDA受体阻断的损害。更普遍地说，结果表明，睡眠和记忆背后的一些脑机制可能有共同的要素。
