Muramyl dipeptide does not induce slow-wave sleep or fever in rats

The synthetic muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), is reported to increase slow-wave sleep and body temperature in cats, rabbits, and squirrel monkeys. The present study examined the ability of MDP to induce sleep and fever in rats. MDP was administered IP at 50, 250 and 500 micrograms/kg. Sleep and body temperature were monitored for 12 hr. MDP failed to affect the duration of wakefulness, S1, S2, or total (S1 + S2) slow-wave sleep. There was also no change in the latency to the first episode of S2 sleep. In contrast, rapid-eye-movement (REM) sleep was significantly suppressed for the first 6 hr after 250 and 500 microgram/kg doses of MDP. There was, however, a rebound increase in REM sleep after the initial period of suppression which resulted in no overall change in the amount of REM sleep. Body temperature was unaffected by MDP. Thus, we conclude that MDP has neither sleep-promoting nor pyrogenic actions in the rat when administered systemically at doses reported to be effective in several other species.