The primary objective of this research proposal is to characterize the role of NMDA, substance P, and the NK1 tachykinin receptor subtype in the generation and entrainment of circadian rhythms.
The specific aims are to determine: 1) the extent that the tachykinin substance P induces or modulates phase shifts of SCN generated circadian rhythms, 2) the extent that the expression of the NK1 tachykinin receptor is necessary for the generation or entrainment of SCN generated circadian rhythms, and 3) the extent that the EAA receptor agonist NMDA can mimic the light induced suppression of nocturnal levels of pineal melatonin The studies will be performed using the Syrian hamster (Mesocricetus auratus). This animal model provides an advantage because it has a highly reproducible wheel-running rhythm and relatively high nocturnal levels of pineal melatonin. The results of the above studies will increase our understanding of the pharmacology of circadian entrainment, and may lead to the development of drugs to combat disorders of the circadian system.
