Research on molecular mechanism of sleep-wakefulness rhythm and development of new hypnotics

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Daily restricted feeding (RF) can produce anticipatory rhythms at both locomotor activity and molecular oscillator level. As orexin Giypocretin) is a neuropeptide playing a critical role in the regulation of both sleep-wake regulation and feeding behavior orexin might be participated in the generation of RF-induced rhythm. In mouse maintained on a 12 h light/dark cycle, preproorexin mRNA and Orexin A protein level in the lateral hypothalamus did not show daily variations under ad loitum but Fos expression in the orexin neurons are high in the night as previously reported. 9 days of daytime RF generated anticipatory daily locomotor activity and shifted the early morning peak of mDbp mRNA rhythm changed to a late evening peak in the cerebral cortex and Caudate putamen. Under these conditions, orexin expression was not changed at mRNA and protein level. However, Fos expression in orexin neuron was higher in the daytime in RF treated mice. On the other hand, expression of two orexin receptors did not show daily variation under ad libitum and RF conditions. In combination of previous work, present results suggest that activity of orexin neuron in the lateral hypothalamus contributes the promotion and maintenance of behavioral activity and feeding behavior.