Analysis Of Rat Sleep Characteristics And Hypnotic Drug Screening Methods To Establish

A good physiological sleep has the function of restoring physical energy and brain energy in human being. However, a sleep evoked by hypnotic (the drug sleep) always has some side effects, such as aggravating the feeling of daze and weariness that caused by insomnia even after the drug sleep. So, if we can bring to light the differences between the physiological sleep and the drug sleep using pharmacological methods, it will be helpful to the development of new safer hypnotic with few side effects.However, domestically most of the pharmacological methods that have been used to screen hypnotic, especially the Chinese medicines, are the behavior experiment methods. They can only provide some preliminary information So, by recording the cortical EEG and the hippocampal EEG in freely moving rats, we developed a method to analyze the properties in the rat sleeps under different conditions using the technology of chronic electrode implanting and the technology of computer signal processing. With this method we compared the properties between the drug sleep evoked by diazepam and the recovery physiological sleep after 8 hours sleep deprivation in rats. The results showed that the time of slow wave sleep and the time of paradoxical sleep significantly increased while the time of wake significantly decreased during both of the two sleep recordings comparing with their baseline recordings. But the switches among 'the different behavior stages appeared more frequently during the diazepam evoked sleeps. The power spectral density (PSD) of EEG during the recovery sleep after sleep deprivation increased significantly. However, the PSD of EEG in lower frequency band significantly decreased in the diazepam sleep comparing with its own baseline sleep And it caused the gravity frequency in the EEG of diazepam sleep shift to the higher frequency. By using the wavelet based time-frequency transition method we analyzed the sleep spindles in EEG during slow wave sleeps. We found that the average duration of the sleep spindle in the diazepam sleep was significantly lengthened, which was similar to the change of the sleep spindles in the intermediate stage when the slow wave sleep transited to the paradoxical sleep. We explained these results with the mechanism of diazepam's action on central nervous system and the mechanism of slow waves and spindles.We also studied the drug sleep after the administration of notoginsenoside , an extractive composition with sedative effect that was got from a kind of Chinese herbal medicine. The results showed that the notoginsenoside could increase the slow wave sleep and lengthen the average duration of each sleep stage. But it did not change the PSD of EEG much.With simultaneously recording of the cortical EEG and the evoked potentials in the dentate gyrus in freely moving rats, we found that under dozing state there was a kind of negative correlation between EPSPs and PSs of the evoked field responses in dentate gyrus. And this phenomenon was correlated with the synchronization and desynchronization of the cortical EEG that induced by the activities of the midbrain reticular formation. After the administration of Urethane, the negative correlation change between EPSPs and PSs was weakened. It may be caused by the mechanism that when the midbrain reticular formation induced cortical desynchronization through the thalamocortical loop, it simultaneously excitated an inhibitory path which acted on the bodies of dentate granule cells and declined the excitability of granule cells. The negative correlation change may be an indication of the activity in the dentate gyrus while the rat natively enters the stage of hypnosis or doze.Other two kinds of hypnotic drug screening method were developed in the paper. One was the jiggle cage test of mouse behavior activity. The other was to assess the effect of a drug on the central nervous system by testing the evoked potential in dentate gyrus after the drug was directly administered intracerebroventricularly. By using the former method we ca...