Effects of L-arginine and SIN-1 on sleep and waking in the rat during both phases of the light-dark cycle.

The effects L-arginine (0.15-0.60 micromol), a nitric oxide precursor, and SIN-1 (3-morpholino-sydnonimine; linsidomine) (0.05-0.2 micromol), a nitric oxide donor, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. L-arginine or SIN-1 given intracerebroventricularly during the light phase of the light-dark cycle induced no significant changes in sleep variables. On the other hand, administration of L-arginine or SIN-1 during the dark phase significantly increased slow wave sleep and reduced waking during the first 4 h of the recording period. The time spent in rapid-eye-movement sleep (REMS) was not significantly modified. The increase of slow wave sleep and/or reduction of waking was already evident during the first 2 h of recording. On the other hand, values of these variables were not different from control values during post-injection hours 5 and 6. Our findings confirm the role of nitric oxide, generated from L-arginine or released from SIN-1, in the regulation of sleep variables in the rat.