Muramyl dipeptide and IL-1 effects on sleep and brain temperature after inhibition of serotonin synthesis

Am J Physiol. 1997 Nov;273(5):R1663-8. doi: 10.1152/ajpregu.1997.273.5.R1663.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / administration & dosage
  • Acetylmuramyl-Alanyl-Isoglutamine / pharmacology*
  • Animals
  • Body Temperature / drug effects
  • Body Temperature / physiology
  • Body Temperature Regulation / drug effects*
  • Body Temperature Regulation / physiology
  • Brain / drug effects
  • Brain / physiology*
  • Cerebral Ventricles / drug effects
  • Cerebral Ventricles / physiology*
  • Darkness
  • Electroencephalography
  • Electromyography
  • Fenclonine / pharmacology*
  • Injections, Intraventricular
  • Interleukin-1 / administration & dosage
  • Interleukin-1 / pharmacology*
  • Light
  • Male
  • Rats
  • Rats, Inbred Strains
  • Serotonin / biosynthesis*
  • Serotonin Agents / pharmacology*
  • Sleep / drug effects*
  • Sleep / physiology

Substances

  • Interleukin-1
  • Serotonin Agents
  • Serotonin
  • Acetylmuramyl-Alanyl-Isoglutamine
  • Fenclonine