Differential sleep modulation by sequentially administered muramyl dipeptide and uridine.

In an attempt to investigate the effects on sleep modulation of order of administration of two substances, sequential intracerebroventricular (ICV) infusions of muramyl dipeptide (MDP, 1.0 nmol) and uridine (5.0 pmol) were conducted in freely behaving rats. To eliminate the influence of intermittent infusions on their behavior, the rats were continuously ICV infused with physiological saline solution, which did not affect their normal sleep-waking dynamics. Under these experimental conditions, uridine infusion (2400-0500 h) attenuated the enhancement of slow-wave sleep (SWS) caused by prior infusion of MDP (1900-2400 h) to the baseline level and, thus, did not exert a sleep-promoting property. In contrast, MDP infusion (2400-0500 h) further potentiated the SWS-enhancing activity of preinfused uridine (1900-2400 h). A single infusion of MDP or uridine (2400-0500 h) similarly enhanced SWS. These results demonstrate that observed differences in the induction and maintenance of sleep are dependent upon the order of exogenously infused uridine and MDP. The time sequence per se of these sleep substances may be responsible for the differential temporal changes in sleep. It is, therefore, assumed that a crucial order of multiple sleep substances may dynamically and differentially regulate sleep in the brain.