| Co-Investigator(Kenkyū-buntansha) |
OSAKA Toshimasa Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Research, 第2研究部, 研究員 (30152101)
SATOH Shinsuke Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Research, 第2研究部, 研究員 (40270574)
WATANABE Kikuko Osaka Bioscience Institute, Department of Molecular Behavioral Biology, Research, 第2研究部, 研究員 (90211672)
URADE Yoshihiro Osaka Bioscience Institute Department of Molecular Behavioral Biology Vice-Head, 第2研究部, 研究副部長 (10201360)
HAYAISHI Osamu Osaka Bioscience Institute Director, 所長 (40025507)
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| Budget Amount *help |
¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1995: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Research Abstract |
Along with the aging of the society in Japan, an increasing number of people is suffering from insomnia in these days, and benzodiazepines are used to treat this symptom. However, these drugs suppress neuronal activities in a non-specific manner, which causes side effects. Therefore, novel drugs which specifically act on sleep-wake regulating mechanisms in the brain are required. Thus, we first have to clarify the brain mechanisms underlying sleep-wake phenomena. In our recent study attempting to do so, the site of action for the sleep-promoting effect of prostaglandin (PG) D_2 was defined in the ventral surface layr of a rostral basal-forebrain region. This basal-forebrain region includes ventral striatum, i.e., the accumbens nucleus and the olfactory tubercle. Further, the brain PGD synthase was shown to be abundantly expressed in the leptomeninges covering the surface of the brain, and the concentration of PGD_2 in the cerebrospinal fluid (CSF) of the rat was found to be higher during the daytime, the sleeping period of the animal, than during the night. Thus, it is inferred that PGD_2 synthesized in the membrane tissues surrounding the ventral surface of the rostral basal forebrain acts at the surface layr of the brain region to initiate sleep. The signals produced by PGD_2 may be transmitted to neural circuits responsible for the sleep-wake regulation. In the process, A_<2a>-adenosine receptors abundantly expressed in the ventral striatum are crucially involved, because CGS21680, an A_<2a>-adenosine agonist, markedly promoted sleep when administered to the same region, whereas KF17837, an A_2-adenosine antagonist, inhibited the sleep promotion produced by PGD_2. These results indicate that adenosine-related as well as PGD_2-related compounds may become novel candidates for the therapeutic drug effective in the treatment of sleep-wake disorders.
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