Ishida Takayuki, Obara Yoshihito, Kamei Chiaki
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
J Pharmacol Sci. 2009 Sep;111(1):44-52. doi: 10.1254/jphs.09142fp. Epub 2009 Aug 29.
We studied the effects of antipsychotics and a hypnotic on sleep disturbance in schizophrenia using an animal model of the disease. Electrodes for the electroencephalogram (EEG) and electromyogram (EMG) were chronically implanted into the cortex and the dorsal neck muscle of rats. EEG and EMG were recorded with an electroencephalograph for 6 h (10:00 - 16:00). SleepSign ver. 2.0 was used for EEG and EMG analysis. Haloperidol and olanzapine had an antagonizing effect on the increases in sleep latency and total awake time and the decrease in total non-rapid eye movement (NREM) sleep time induced by MK-801. Olanzapine also antagonized the decrease in total rapid eye movement (REM) sleep time induced by MK-801. Aripiprazole antagonized only the increase in sleep latency induced by MK-801, whereas, risperidone, quetiapine, and flunitrazepam had no effect in the changes of sleep-wake pattern induced by MK-801. Olanzapine increased delta activity and decreased beta activity during NREM sleep. In contrast, flunitrazepam had an opposite effect. It was clarified that haloperidol and olanzapine were effective for decrease of sleep time in this animal model of schizophrenia. In addition, aripiprazole showed a sleep-inducing effect in schizophrenia model rat. On the other hand, flunitrazepam showed no beneficial effect on sleep disturbance in schizophrenia model rat.
我们使用该疾病的动物模型研究了抗精神病药物和一种催眠药对精神分裂症睡眠障碍的影响。将脑电图(EEG)和肌电图(EMG)电极长期植入大鼠的皮层和颈部背侧肌肉。用脑电图仪记录EEG和EMG 6小时(10:00 - 16:00)。使用SleepSign ver. 2.0进行EEG和EMG分析。氟哌啶醇和奥氮平对MK-801诱导的睡眠潜伏期延长、总清醒时间增加以及总非快速眼动(NREM)睡眠时间减少具有拮抗作用。奥氮平还拮抗了MK-801诱导的总快速眼动(REM)睡眠时间减少。阿立哌唑仅拮抗MK-801诱导的睡眠潜伏期延长,而利培酮、喹硫平和氟硝西泮对MK-801诱导的睡眠-觉醒模式变化没有影响。奥氮平增加了NREM睡眠期间的δ波活动并降低了β波活动。相比之下,氟硝西泮具有相反的作用。已阐明氟哌啶醇和奥氮平在这种精神分裂症动物模型中对减少睡眠时间有效。此外,阿立哌唑在精神分裂症模型大鼠中显示出促睡眠作用。另一方面,氟硝西泮对精神分裂症模型大鼠的睡眠障碍没有有益作用。