Effect of ethanol on sleep-awake state in sleep-disturbed rats.

The present study was undertaken to investigate the effect of ethanol on the sleep-wake cycle in normal rats and sleep-disturbed rats. In normal rats, no significant difference was observed by ethanol in sleep latency, total awake time and total non-rapid eye movement (NREM) sleep time, except for total REM sleep time. On the other hand, in sleep-disturbed rats, ethanol at doses of 1 and 2 g/kg caused significant decreases in sleep latency and total wake time, and an increase in total NREM sleep time. In addition, ethanol showed a significant increase in delta activity in the sleep-disturbed model rat, different from triazolam. These results suggested that ethanol had not only a hypnotic but also a sleep-maintaining effect in sleep-disturbed rats at reasonable blood ethanol concentrations.

Studies on wakefulness-promoting effect of memantine in rats.

We hypothesized that memantine, an anti-dementia drug, may be useful for the treatment of excessive daytime sleepiness. The effect of memantine on excessive sleepiness after 6 h sleep deprivation was studied in comparison with that of methylphenidate, and the involvement of the dopaminergic system in the wakefulness-promoting effect of memantine was also evaluated. Electrodes for electroencephalogram (EEG) and electromyogram (EMG) were chronically implanted into the cortex and dorsal neck muscle, respectively, of adult male rats. EEG and EMG were recorded with an electroencephalograph for 6 h (19:00-01:00). After sleep deprivation (13:00-19:00), compensatory excessive sleepiness (19:00-01:00) was observed in rats. Memantine (10 mg/kg, p.o.) and methylphenidate (10-30 mg/kg, p.o.) caused a significant increase of sleep latency compared with the control group. Furthermore, a significant increase in total awake time and significant decreases in total non-rapid eye movement (NREM) sleep and REM sleep times were observed by administration of memantine (3-10 mg/kg) and methylphenidate (3-30 mg/kg) compared with control in sleep deprivation rats. Although the effect of memantine was significantly suppressed by D1 receptor antagonist SCH 23390 (0.1 mg/kg, i.p.), D2 receptor antagonist raclopride had no antagonistic effect (1 mg/kg, i.p.). From these results, the effect of memantine on sleepiness after sleep deprivation was similar to that of methylphenidate, and D1 receptor may be involved in the effect of memantine.

Hypnotic and sleep quality-enhancing properties of kavain in sleep-disturbed rats.

The present study was performed to investigate the effects of kavain on the sleep-wake cycle in comparison with that of rilmazafone and diphenhydramine using sleep-disturbed rats. Electrodes for the electroencephalogram (EEG) and electromyogram (EMG) were implanted into Wistar rats. Total awake time, non-rapid eye movement (non-REM) sleep and rapid eye movement (REM) sleep were measured for 6 h. Kavain and rilmazafone showed a significant shortening in sleep latency, decreased awake time, and increased non-REM sleep time. On the other hand, significant shortening of the sleep latency was observed following the administration of diphenhydramine, while no effects were observed on the awake and non-REM sleep time. Moreover, kavain showed a significant increase in delta activity during non-REM sleep in sleep-disturbed rats, whereas a significant decrease in delta power during non-REM sleep was observed with rilmazafone. These results clearly indicate that kavain is a compound with not only hypnotic effects, but also sleep quality-enhancement effects.

Effects of some antipsychotics and a benzodiazepine hypnotic on the sleep-wake pattern in an animal model of schizophrenia.

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.

Effects of histamine H1-antagonists on sleep-awake state in rats placed on a grid suspended over water or on sawdust.

The present study was performed to investigate the effects of histamine H(1)-antagonists on the sleep-awake state in rats placed on a grid suspended over water in comparison with rats placed on sawdust. When rats were placed on the grid suspended over water, significant increases in the awake time and decreases in non-rapid eye movement (non-REM) sleep time were observed compared with in rats on sawdust, even when measured hourly for 6 h. Diphenhydramine, chlorpheniramine and promethazine caused a significant decrease in the awake time and increase in non-REM sleep time in rats placed on the grid suspended over water for 1-2 h and/or 2-3 h after administration. On the other hand, in rats placed on sawdust, no significant differences were observed in the awake time and non-REM sleep time with diphenhydramine and chlorpheniramine compared with the control. Different from these two drugs, promethazine caused a significant decrease in the awake time and increase in non-REM sleep time 1-2 h and 2-3 h after administration even when rats were placed on sawdust at a relatively high dose. These results clearly indicate that histamine H(1)-antagonists had potent effects on decreasing the awake time and increasing non-REM sleep time under the conditions of an activated histaminergic system.