NITRIC-OXIDE SYNTHASE INHIBITOR BLOCKS LIGHT-INDUCED PHASE-SHIFTS OF THE CIRCADIAN ACTIVITY RHYTHM, BUT NOT C-FOS EXPRESSION IN THE SUPRACHIASMATIC NUCLEUS OF THE SYRIAN-HAMSTER

Circadian rhythms in mammals are entrained to the environmental light cycle by daily adjustments in the phase of the circadian pacemaker loc ated in the suprachiasmatic nuclei (SCN) of the hypothalamus. Brief ex posure of hamsters maintained under constant darkness to ambient light during subjective nighttime produces both phase shifts of the circadi an activity rhythm and characteristic patterns of c-fos protein (Fos) immunoreactivity in the SCN. In this study, we demonstrate that light- induced phase shifts of the circadian activity rhythm are blocked by i ntracerebroventricular (i.c.v.) injection of the competitive nitric ox ide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME) , but not by the inactive isomer, D-NAME. The effects of L-NAME are re versible and dose-related, and are countered by co-injection of argini ne, the natural substrate for NOS. While effects on behavioral rhythms are pronounced, similar treatment does not alter the pattern of light -induced Fos immunoreactivity in the SCN. These results suggest that n itric oxide is a component of the signal transduction pathway that com municates photic information to the SCN circadian pacemaker, and that nitric oxide production is either independent of, or downstream from, pathways involved in induction of c-fos expression.