Muramyl dipeptide and IL-1 effects on sleep and brain temperature after inhibition of serotonin synthesis.
The role of the interactions between serotonin (5-HT) and muramyl dipeptide (MDP) and interleukin-1 (IL-1) in sleep control and thermoregulation was evaluated. To this purpose, MDP and IL-1 were injected intracerebroventricularly at dark onset into freely moving rats pretreated twice intraperitoneally with para-chlorophenylalanine (PCPA) (300 mg/kg), which depletes brain 5-HT and causes insomnia. Fever and slow-wave sleep (SWS) enhancement induced by 150 pmol MDP were completely blocked in PCPA-pretreated rats. Only the first phase of the biphasic increase in SWS induced by 2.5 ng IL-1 was suppressed by PCPA pretreatment, whereas fever remained unaffected. These results suggest that 1) MDP effects on both sleep-wake activity and brain cortical temperature are mediated by the serotonergic system; 2) the mechanisms mediating the first and the second phases of IL-1-induced SWS excess are different: 5-HT could be involved in the first phase, but not in the second one; and 3) the 5-HT system does not appear to be involved in IL-1-induced fever.
Imeri
L
L
Istituto di Fisiologia Umana II, Universitá degli Studi, Milan, Italy.
Bianchi
S
S
Mancia
M
M
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003624:Darkness; D004569:Electroencephalography; D004576:Electromyography; D010134:Fenclonine / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008027:Light; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000096:biosynthesis*; D018490:Serotonin Agents / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects* / Q000502:physiology
D007375:Interleukin-1; D018490:Serotonin Agents; D012701:Serotonin; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D010134:Fenclonine