Muramyl dipeptide-induced sleep and fever: effects of ambient temperature and time of injections.
Sleep-promoting factors isolated from rabbit brain and human urine enhance slow-wave sleep (SWS) when administered to rabbits and other mammalian species. These substances were identified as muramyl peptides (MPs). A simple synthetic chemical analogue to these substances, N-acetylmuramyl-L-alanyl-D-isoglutamine (or MDP for muramyl dipeptide), was also found to enhance SWS. MDP is also pyrogenic and can alter rapid eye movement (REM) sleep. However, the effects of MDP on rabbit REM sleep and the relationship between thermoregulation and MDP-altered sleep have not been investigated. We tested, therefore, MDP in rabbits. We found that 1) intracerebroventricular administration of 125 pmol of MDP reduced REM sleep time from 10 +/- 3% of total recording time after vehicle to 4 +/- 3%; 2) a stereoisomer of MDP, N-acetylmuramyl-D-alanyl-D-isoglutamine, failed to have any effects on the sleep and temperature parameters measured; 3) acute elevation of ambient temperature from 21 to 27 degrees C enhanced SWS (37 +/- 3-55 +/- 3%) but not REM sleep; 4) at 27 degrees C MDP further enhanced SWS to 67 +/- 3% and its REM sleep suppression effect persisted; and 5) intravenously injected MDP had greater effects on body temperature during light hours than if administered during dark hours. We conclude that MDP reduces REM sleep in rabbits, that its effects on thermoregulatory processes depend on the time of injection, and that the effects of the thermoregulatory process on sleep are independent of, in part, the effects of MDP on sleep.
Shoham
S
S
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163.
Krueger
J M
JM
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004569:Electroencephalography; D004576:Electromyography; D005334:Fever / Q000139:chemically induced*; D007276:Injections, Intraventricular; D008297:Male; D011817:Rabbits; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D013696:Temperature; D013997:Time Factors
D000119:Acetylmuramyl-Alanyl-Isoglutamine