Datta S, Patterson E H, Spoley E E
Sleep Research Laboratory, Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
J Neurosci Res. 2001 Oct 1;66(1):109-16. doi: 10.1002/jnr.1202.
Microinjection of the excitatory amino acid, L-glutamate into the brainstem pedunculo pontine tegmentum (PPT) has been shown to induce wakefulness, however, it has been unclear that receptors mediate this effect. The aim of this study was to test the hypothesis that in the PPT, L-glutamate induces cortical activation and wakefulness via activation of NMDA receptors. To test this hypothesis, three sets of micro-injections into the PPT were carried out on two different groups of rats that were then allowed to move freely although chronic instrumentation recorded sleep/wake states. Three days after the initial control injections of saline, in a contra-lateral site, Group I was micro-injected with saline + glutamate (saline first, and glutamate 15 min later); after another 3 days, the same rats were micro-injected with the NMDA-receptor-specific antagonist, 2-amino-5-phosphonopentanoic acid, (AP5) + glutamate. Group II received the same initial control injections (saline only), then AP5 + glutamate and the saline + glutamate micro-injections last. In rats that were not pretreated with AP5, microinjection of a 90 ng dose of L-glutamate (0.48 nmol in a volume of 0.1 microl vehicle) kept animals awake for 2-3 hr by eliminating both slow-wave sleep (SWS) and rapid eye movement (REM) sleep. These behavioral state changes were accompanied by concomitant increase in the power of gamma (gamma) frequency (20-60 Hz) waves in the cortical EEG. Pretreatment of L-glutamate injection sites with 0.48 nmol of AP5 blocked L-glutamate-induced-wakefulness and preserved a normal amount of wakefulness and sleep. Pretreatment with AP5 decreased the power of gamma-wave activity below its control level. These results support the hypothesis that the glutamate-induced-wakefulness and cortical activation effects are mediated via the NMDA receptors.
向脑干脚桥被盖区（PPT）微量注射兴奋性氨基酸L-谷氨酸已被证明可诱导觉醒，然而，介导这种效应的受体尚不清楚。本研究的目的是检验以下假设：在PPT中，L-谷氨酸通过激活N-甲基-D-天冬氨酸（NMDA）受体诱导皮层激活和觉醒。为了验证这一假设，对两组不同的大鼠进行了三组向PPT的微量注射，然后让它们自由活动，同时通过慢性植入仪器记录睡眠/觉醒状态。在最初注射生理盐水作为对照三天后，在对侧部位，第一组大鼠先微量注射生理盐水，15分钟后再注射谷氨酸；再过三天，对同一批大鼠微量注射NMDA受体特异性拮抗剂2-氨基-5-磷酸戊酸（AP5）+谷氨酸。第二组大鼠接受相同的初始对照注射（仅生理盐水），然后先注射AP5 +谷氨酸，最后注射生理盐水+谷氨酸。在未用AP5预处理的大鼠中，微量注射90 ng剂量的L-谷氨酸（0.48 nmol，溶于0.1微升载体中）可消除慢波睡眠（SWS）和快速眼动（REM）睡眠，使动物保持清醒2 - 3小时。这些行为状态的变化伴随着皮层脑电图中γ（γ）频率（20 - 60 Hz）波功率的相应增加。用0.48 nmol的AP5预处理L-谷氨酸注射部位可阻断L-谷氨酸诱导的觉醒，并保持正常的觉醒和睡眠时间。用AP5预处理可使γ波活动的功率降至对照水平以下。这些结果支持了以下假设：谷氨酸诱导的觉醒和皮层激活效应是通过NMDA受体介导的。
