Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Sleep. 2012 Jul 1;35(7):1011-6. doi: 10.5665/sleep.1972.
Sub-anesthetic doses of NMDA receptor antagonists suppress sleep and elicit continuous high-power gamma oscillations lasting for hours. This effect is subunit-specific, as it was also seen after preferential blockade of the NR2A but not of the NR2B subunit-containing receptors. The objective of this study was to test whether NR2B receptor antagonists that do not induce lasting aberrant gamma elevation affect gamma activity during specific behaviors and states, including REM sleep, when gamma normally occurs.
Gamma oscillations in cortical EEG were assessed in different vigilance states in rats and were compared before and after injection of nonselective (ketamine, 10 mg/kg, and MK801, 0.2 mg/kg), as well as NR2A-preferring (NVP-AAM077, 20 mg/kg), and NR2B-selective NMDA receptor antagonists (Ro25-6985, 10 mg), and vehicle.
In contrast to nonselective and NR2A-preferring antagonists, Ro25-6985 did not disrupt sleep and had no effect on gamma activity during waking and slow wave sleep. It significantly increased, however, gamma power in the frontal (but not in occipital) cortex during REM sleep (by 37% ± 10%, average in the first 4 h). The effect had a short onset; enhanced gamma activity appeared as early as in the first REM sleep episode post-injection and lasted over 8 hours. Increased gamma power induced by MK-801 (46% ± 5%) and NVP-AAM077 (100% ± 8%) during REM sleep could also be detected several hours after injection when periodic alternation of sleep-wake states returned.
By acting on gamma oscillations in a state-dependent manner, NMDA receptors might have subunit-specific role in REM sleep-associated cognitive processes.
亚麻醉剂量的 NMDA 受体拮抗剂可抑制睡眠并引发持续数小时的高功率伽马振荡。这种效应具有亚基特异性，因为在优先阻断 NR2A 亚基而不是 NR2B 亚基的受体后，也观察到了这种效应。本研究的目的是测试是否不会引起持续异常伽马升高的 NR2B 受体拮抗剂会影响特定行为和状态（包括 REM 睡眠，即正常发生伽马的状态）期间的伽马活动。
在大鼠的不同警戒状态下评估皮质 EEG 的伽马振荡，并在注射非选择性（氯胺酮，10mg/kg 和 MK801，0.2mg/kg）以及 NR2A 优先（NVP-AAM077，20mg/kg）和 NR2B 选择性 NMDA 受体拮抗剂（Ro25-6985，10mg）前后进行比较。
与非选择性和 NR2A 优先拮抗剂相反，Ro25-6985 不会破坏睡眠，并且在觉醒和慢波睡眠期间对伽马活动没有影响。然而，它显著增加了 REM 睡眠期间额（但不是枕）皮质的伽马功率（增加 37%±10%，平均在前 4 小时）。该效应的起始时间很短；在注射后的第一个 REM 睡眠发作中就出现了增强的伽马活动，并持续了 8 个多小时。MK-801（46%±5%）和 NVP-AAM077（100%±8%）在 REM 睡眠期间诱导的伽马功率增加也可以在注射后数小时检测到，当时睡眠-觉醒状态的周期性交替恢复。
NMDA 受体以状态依赖的方式作用于伽马振荡，可能在 REM 睡眠相关认知过程中具有亚基特异性作用。
