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 located in the suprachiasmatic nuclei (SCN) of the hypothalamus. Brief exposure of hamsters maintained under constant darkness to ambient light during subjective nighttime produces both phase shifts of the circadian 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 intracerebroventricular (i.c.v.) injection of the competitive nitric oxide 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 reversible and dose-related, and are countered by co-injection of arginine, 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 nitric oxide is a component of the signal transduction pathway that communicates 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.
Weber
E T
ET
BRAIN Research Institute, Armstrong Laboratory, Brooks AFB, TX 78235, USA.
Gannon
R L
RL
Michel
A M
AM
Gillette
M U
MU
Rea
M A
MA
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects*; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008647:Mesocricetus; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010775:Photic Stimulation; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D013493:Suprachiasmatic Nucleus / Q000378:metabolism* / Q000502:physiology
D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester