EFFECT OF A NITRIC-OXIDE SYNTHASE INHIBITOR, N-NITRO-L-ARGININE METHYLESTER, ON LIGHT-INDUCED PHASE DELAY OF CIRCADIAN-RHYTHM OF WHEEL-RUNNING ACTIVITY IN GOLDEN-HAMSTERS

Under constant darkness hamsters demonstrate free-running activity rhythms and light exposure during the early subjective night results in permanent phase delays of the activity rhythm. Recently, we reported that application of glutamate receptor agonists such as N-methyl-D-aspartate could reset the phase of the circadian rhythm of suprachiasmatic nucleus firing activity in vitro via nitric oxide production. In order to confirm this result by in vivo experiment, we examined the effect of nitric oxide synthesis inhibitor on the light-induced phase delay of circadian rhythms of wheel-running activity in hamsters. In vehicle-treated animals, light stimulation at circadian time 13.5 resulted in stable phase delays (1.3 +/- 0.63 h), whereas pre-treatment with 150 mg/kg of N-nitro-L-arginine methylester (L-NAME) significantly attenuated light-induced phase delays (0.72 +/- 0.18 h). L-NAME administration alone without light exposure, did not cause phase changes. The L-NAME-induced attenuating effect was reversed by co-administration of L-arginine (300 mg/kg). The present results suggest that nitric oxide production is involved in the light-induced phase delay of the hamster's circadian system.