Changes of sleep patterns in rats with chronic constriction injury under aversive conditions.

In the present study, we investigated the changes of sleep parameters in rats with chronic constriction injury (CCI) under aversive conditions. The electroencephalogram (EEG) in the frontal cortex of CCI rats and electromyogram (EMG) were measured over 6 h by placing rats on sandpaper as an aversive condition, to compare with rats placed on sawdust. Six days after CCI surgery, the rats exhibited significant mechanical allodynia, and also had neuropathic pain. When rats were placed on sawdust, no significant difference was observed between the CCI group and sham-operated control group in sleep latency, total waking time, total non-REM sleep time and total REM sleep time. On the other hand, when CCI rats were placed on sandpaper, a significant increase was observed in sleep latency and total waking time compared with the sham group; however, no significant difference was observed in the total non-REM sleep time and total REM sleep time between these two groups. These results indicate that an important factor of sleep disturbance in CCI rats is not only damage to the nerves but also being under aversive conditions. In addition, it was found that CCI rats placed on sandpaper as an aversive condition can serve as a new sleep disturbance model.

Effect of tandospirone on sleep latency in rats placed on a grid suspended over water.

The present study was performed to examine the effect of tandospirone on sleep latency in a new insomnia animal model by placing rats on a grid suspended over water. For investigating the mechanism of tandospirone, the effect of tandospirone on sleep latency was also studied using rats that were depleted with neuronal serotonin (5-HT) after p-chlorophenylalanine administration. Tandospirone caused a shortening of sleep latency dose-dependently, and a significant effect was observed at 20 mg/kg, p.o. or more. A shortening of sleep latency was observed by administration of p-chlorophenylalanine (300 mg/kg, i.p.) for 2 days. On the other hand, tandospirone exerted no potentiating effect on the shortening of sleep latency induced by p-chlorophenylalanine. From these findings, a shortening of sleep latency induced by tandospirone may occur through the pre-synaptic 5-HT(1A) receptors in rats.

[Effect of santalol on the sleep-wake cycle in sleep-disturbed rats].

Sandalwood oil is widely used in aromatherapy for alleviating various symptoms. Santalol, a major component of sandalwood oil, has been reported to have central nervous system depressant effects such as sedation. In the present study, we investigated the effect of santalol on the sleep-wake cycle in sleep-disturbed rats. When inhaled at a concentration of 5 X 10(-2) ppm, santalol caused a significant decrease in total waking time and an increase in total non-rapid eye movement (NREM) sleep time. In order to clarify the mechanism of action, olfactory hypofunction was caused in rats by intranasal application of 5% zinc sulfate solution, and thereafter the effects of inhalation of fragrances were evaluated. In this study, it was found that the impairment of the olfactory system showed no significant effect on the changes in sleep parameters induced by santalol. This result suggests that santalol may act via the circulatory system rather than the olfactory system. That is, santalol is thought to be absorbed into the blood through the respiratory mucosa, and then exert its action. From these results, it is concluded that santalol may be useful in patients having difficulty maintaining sleep without being affected by individual differences in perfume-related preference.

Hypnotic activities of chamomile and passiflora extracts in sleep-disturbed rats.

In the present study, we investigated hypnotic activities of chamomile and passiflora extracts using sleep-disturbed model rats. A significant decrease in sleep latency was observed with chamomile extract at a dose of 300 mg/kg, while passiflora extract showed no effects on sleep latency even at a dose of 3000 mg/kg. No significant effects were observed with both herbal extracts on total times of wakefulness, non-rapid eye movement (non-REM) sleep and REM sleep. Flumazenil, a benzodiazepine receptor antagonist, at a dose of 3 mg/kg showed a significant antagonistic effect on the shortening in sleep latency induced by chamomile extract. No significant effects were observed with chamomile and passiflora extracts on delta activity during non-REM sleep. In conclusion, chamomile extract is a herb having benzodiazepine-like hypnotic activity.

Effects of kava-kava extract on the sleep-wake cycle in sleep-disturbed rats.

RATIONALE: Kava-kava extract may be useful as an herbal medicine for treatment of insomnia and anxiety. OBJECTIVES: The present study was undertaken to investigate the effects of kava-kava extract on the sleep-wake cycle in comparison with that of flunitrazepam using sleep-disturbed rats. METHODS: Electrodes for measurement of electroencephalogram (EEG) and electromyogram (EMG) were implanted into the frontal cortex and the dorsal neck muscle of rats. EEG and EMG were recorded with an electroencephalogram. SleepSign ver.2.0 was used for EEG and EMG analysis. Total times of wakefulness, non-rapid eye movement (non-REM) and REM sleep were measured from 09:00 to 15:00. RESULTS: A significant shortening of the sleep latency in sleep-disturbed rats was observed following the administration of kava-kava extract at a dose of 300 mg/kg, while no effects were observed on the total waking and non-REM sleep time. On the other hand, flunitrazepam showed a significant shortening in sleep latency, decrease in total waking time and increase in total non-REM sleep time. Although the effects of flunitrazepam were antagonized by the benzodiazepine receptor antagonist flumazenil, the effect of kava-kava extract was not antagonized by flumazenil. Kava-kava extract 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 flunitrazepam. Flumazenil caused no significant effect on the changes in delta activity induced by both kava-kava extract and flunitrazepam. CONCLUSIONS: Kava-kava extract is an herbal medicine having not only hypnotic effects, but also sleep quality-enhancement effects.

Effects of three hypnotics on the sleep-wakefulness cycle in sleep-disturbed rats.

RATIONALE: New sleep disturbance model in rats is useful for estimating the characteristics of some hypnotics. OBJECTIVES: The present study was undertaken to investigate the utility of a sleep disturbance model by placing rats on a grid suspended over water using three kinds of hypnotics, that is, short-acting benzodiazepine (triazolam), intermediate-acting benzodiazepine (flunitrazepam) and long-acting barbiturate (phenobarbital). METHODS: Electrodes for measurement of EEG and EMG were implanted into the frontal cortex and the dorsal neck muscle of rats. EEG and EMG were recorded with an electroencephalogram. SleepSign ver.2.0 was used for EEG and EMG analysis. Total times of wakefulness, non-REM and REM sleep were measured from 0900 to 1500 hours. RESULTS: In rats placed on the grid suspended over water up to 1 cm under the grid surface, not only triazolam but also flunitrazepam and phenobarbital caused a shortening of sleep latency. Both flunitrazepam and phenobarbital were effective in increasing of total non-REM sleep time in rats placed on sawdust or the grid, and the effects of both drugs in rats placed on the grid were larger than those in rats placed on sawdust. Measurement of the hourly non-REM sleep time was useful for investigating the peak time and duration of effect of the three hypnotics. Phenobarbital showed a decrease in total REM sleep time in rats placed on the grid, although both triazolam and flunitrazepam were without effect. CONCLUSIONS: The present insomnia model can be used as a sleep disturbance model for testing not only the sleep-inducing effects but also the sleep-maintaining effects including non-REM sleep and REM sleep of hypnotics.