Muramyl Peptide-Enhanced Sleep: Pharmacological Optimization of Performance
Abstract
Previous research on sleep-promoting substances that accumulate in cerebrospinal fluid during wakefulness led to the discovery of the somnogenic activity of muramyl peptides (MPs). Our broad goal is to develop information needed to ascertain if MPs or other endogenous sleep factors would be practical as somnogenic agents. We report on: 1) Murametide, an MP that induces interleukin-1 (IL1) production but also blocks IL1-induced fevers, potentiated IL1-induced fever and sleep when given at the same time as IL1. In contrast, when IL1 was given 30 min after murametide, murametide completely blocked IL1- induced fevers but still potentiated IL1-induced sleep. 2) Previously, we proposed that MP induced sleep via a step involving IL1 production. IL1 also induces corticotropic-releasing factor (CRF) release, which leads to enhanced adreno-corticotropic hormone (ACTH) release and glucocorticoid release. Last year we showed that alpha melanocyte-stimulating hormone (i.e., ACTH(1-13)) blocked IL1-induced sleep responses. Since it was known that glucocorticoids turn off IL1 production, we tested CRF in combination with IL1. CRF blocked IL1- enhanced sleep. 3) Several of the cytokines whose production are enhanced by MPs, IL1, interferon alpha2, and tumor necrosis factor, are pyrogenic and somnogenic. 4) We showed that prolactin and two of its hypothalamic releasing factors, selectively enhanced REM sleep. (edc)
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1989
- Accession Number
- ADA219749
Entities
People
- James M. Krueger
Organizations
- University of Tennessee