Bacterial peptidoglycans as modulators of sleep. II. Effects of muramyl peptides on the structure of rabbit sleep

Sleep-promoting substances derived from human urine and rabbit brain were identified as muramyl peptides (MPs). We report in the accompanying paper that in the molecular structure of MPs, the 1,6-anhydro muramic acid moiety of MPs is important for enhancement of slow-wave sleep (SWS) in rabbits. Here, we document more extensively the effects of one MP: 1,6-anhydro-muramyl-alanyl-glutamyl-diaminopimelyl-alanine (AMTP for anhydro-muramyl tetrapeptide) on sleep structure of rabbits. AMTP significantly increased percent of time spent in SWS but its effects on rapid eye movement (REM) sleep were dose-dependent. Brain temperatures were significantly elevated but continued to fluctuate with sleep and wake state transitions indistinguishably from control. Sleep was episodic and animals could be easily aroused. AMTP increased number of SWS episodes and decreased number of REM episodes. There was a shift in the distribution of sleep-wake episode durations: longer waking and REM episodes were decreased, thus increased the proportion of shorter episodes. Increased duration of SWS resulted from a larger number of SWS episodes longer than 8 min. We conclude that AMTP amplifies the SWS compenent of physiological sleep.