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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS041857-02
Application #
6402874
Study Section
Special Emphasis Panel (ZRG1-ALTX-4 (03))
Program Officer
Nichols, Paul L
Project Start
2001-09-30
Project End
Budget Start
2001-09-30
Budget End
2002-09-29
Support Year
2
Fiscal Year
2001
Total Cost
$33,075
Indirect Cost
Name
Georgia State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
837322494
City
Atlanta
State
GA
Country
United States
Zip Code
30302
Novak, Colleen M; Ehlen, J Christopher; Paul, Ketema N et al. (2006) Light and GABA)(A) receptor activation alter period mRNA levels in the SCN of diurnal Nile grass rats. Eur J Neurosci 24:2843-52
Gamble, Karen L; Paul, Ketema N; Karom, Mary C et al. (2006) Paradoxical effects of NPY in the suprachiasmatic nucleus. Eur J Neurosci 23:2488-94
Paul, Ketema N; Fukuhara, Chiaki; Karom, Mary et al. (2005) AMPA/kainate receptor antagonist DNQX blocks the acute increase of Per2 mRNA levels in most but not all areas of the SCN. Brain Res Mol Brain Res 139:129-36
Paul, Ketema N; Gamble, Karen L; Fukuhara, Chiaki et al. (2004) Tetrodotoxin administration in the suprachiasmatic nucleus prevents NMDA-induced reductions in pineal melatonin without influencing Per1 and Per2 mRNA levels. Eur J Neurosci 19:2808-14
Paul, K N; Fukuhara, C; Tosini, G et al. (2003) Transduction of light in the suprachiasmatic nucleus: evidence for two different neurochemical cascades regulating the levels of Per1 mRNA and pineal melatonin. Neuroscience 119:137-44