Lancel M, Crönlein T A, Faulhaber J
Max-Planck Institute of Psychiatry, Clinical Institute, Munich, Germany.
Neuropsychopharmacology. 1996 Jul;15(1):63-74. doi: 10.1016/0893-133X(95)00157-9.
To assess the influence of the gamma-aminobutyric acid (GABA)A receptor on sleep and sleep EEG, rats were injected intraperitoneally with vehicle, two doses of muscimol (0.2 and 0.4 mg/kg), a selective GABAA agonist, and midazolam (3 mg/kg), a benzodiazepine-GABAA agonist. EEG and EMG recordings were made for 6 or 8 hours. Muscimol dose-dependently increased the amount of nonrapid eye movement sleep (nonREMS) and REMS. The higher dose of muscimol enhanced EEG activity over almost the entire frequency range (0.5-25 Hz), including delta (0.5-4 Hz) and sigma (11-16 Hz) activity, within nonREMS and in the frequencies over 10 Hz within REMS. Midazolam also increased the amount of nonREMS. However, most of the other effects of midazolam contrasted the effects of muscimol: midazolam decreased REMS, reduced low frequency (< or = 11 Hz) EEG activity within nonREMS, and enhanced the activity in higher frequencies during both nonREMS and REMS. These data demonstrate the involvement of GABAA receptors in the regulation of sleep-wake behavior as well as in the generation of spindles and delta waves during nonREMS. The effects of these two GABAA agonists indicate that activation of different binding sites on the GABAA receptor complex differentially affect sleep states and sleep EEG.
为评估γ-氨基丁酸（GABA）A受体对睡眠及睡眠脑电图的影响，给大鼠腹腔注射溶媒、两种剂量的蝇蕈醇（0.2和0.4毫克/千克）（一种选择性GABAA激动剂）以及咪达唑仑（3毫克/千克）（一种苯二氮䓬-GABAA激动剂）。进行6或8小时的脑电图和肌电图记录。蝇蕈醇剂量依赖性地增加非快速眼动睡眠（nonREMS）和快速眼动睡眠（REMS）的时长。较高剂量的蝇蕈醇增强了几乎整个频率范围（0.5 - 25赫兹）的脑电图活动，包括nonREMS期间的δ波（0.5 - 4赫兹）和σ波（11 - 16赫兹）活动以及REMS期间超过10赫兹的频率活动。咪达唑仑也增加了nonREMS的时长。然而，咪达唑仑的大多数其他效应与蝇蕈醇的效应相反：咪达唑仑减少了REMS，降低了nonREMS期间的低频（≤11赫兹）脑电图活动，并增强了nonREMS和REMS期间较高频率的活动。这些数据表明GABAA受体参与了睡眠 - 觉醒行为的调节以及nonREMS期间纺锤波和δ波的产生。这两种GABAA激动剂的效应表明，GABAA受体复合物上不同结合位点的激活对睡眠状态和睡眠脑电图有不同的影响。
