Artificial regulation of the sleep-wake state of an experimental animal (rat).

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The aim of this research project was to develop and establish a method of artificial regulation of the sleepwake state of an experimental animal. This project was important in achieving the ultimate purposes of our study to understand the regulatory mechanism of sleep-wake activities and consciousness and to clarify the meaning of sleep. The results of this project will be useful, as well, in developing a new medicine and/or technique for the treatment of sleep-wake disorders in man.The results of this research project indicate that, in order to artificially regulate the physiological state of sllep and wakefulness, prostaglandin (PG) D_2 and inhibitors of PGD synthase can be useful probes. When PGD_2 was infused continuously into the subarachnoid space just under the rostal basal forebrain, the slow-wave sleep extraordinarily increased up to the maximum level following a 30-min latency in rats. The sleeping state brought about by PGD_2 was indistinguishable from the natural sleep of the rats. On the other hand, when a PGD-synthase inhibitor, e.g., an inorganic quadrivalent selenium compound, was continuously administered to the rostral basal-forebrain area via a microdialysis probe that had been chronically implanted in the brain, sleep was almost completely suppressed following 2-hours latency. Such extraordinary effects could not obtained in rats with other products in the arachidonate cascade or serotonin and its related compounds, the latter of which have been actively studied for the physiological implication of serotonin in the brain sleep-wake regulatory mechanisms.Our results also indicate that not only agonists and antagonists but compounds that inhibit the PGD synthase activity also have advantages in designing new drugs of the treatment of sleep-wake disorders.