CGMP-DEPENDENT PROTEIN-KINASE INHIBITOR BLOCKS LIGHT-INDUCED PHASE ADVANCES OF CIRCADIAN-RHYTHMS IN-VIVO

The suprachiasmatic nucleus (SCN) contains the primary mammalian circa dian clock. Light synchronizes these circadian rhythms through a mecha nism involving the release of excitatory amino acids (EAA) and synthes is of nitric oxide (NO) in the SCN. In the current study, we investiga ted whether cGMP-mediated activation of cGMP-dependent protein kinase (PKG) is associated with light-induced phase shifts of the circadian o scillator. Local administration of the specific PKG inhibitor, KT-5823 , significantly attenuated light-induced advances in the phase of acti vity rhythms when administered during late subjective night (CT 19). S imilar treatment at CT 14 had no significant effect on light-induced p hase delays. These results are the first to implicate PKG in the bioch emical pathway(s) responsible for photic phase advances, and suggest a divergence in biochemical pathways involved in photic phase shifts.