Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Oct;81(19):6240–6244. doi: 10.1073/pnas.81.19.6240

Differential sleep-promoting effects of five sleep substances nocturnally infused in unrestrained rats.

S Inoué, K Honda, Y Komoda, K Uchizono, R Ueno, O Hayaishi
PMCID: PMC391896  PMID: 6592612

Abstract

Sleep-inducing and sleep-maintaining effects of five different putative sleep substances were compared by the same nocturnal 10-hr intracerebroventricular infusion technique in otherwise saline-infused, freely moving male rats. Delta-sleep-inducing peptide (2.5 nmol), which induces electroencephalogram delta (slow)-wave patterns, was rapidly effective in increasing both slow-wave sleep and paradoxical sleep but the effects were not long-lasting. Muramyl dipeptide (2 nmol) induced excessive slow-wave sleep in the middle of the infusion period, accompanying a simultaneous elevation of brain temperature. However, paradoxical sleep was not affected. Component B of sleep-promoting substance (2 brainstem equivalents), a partially purified extract from rats deprived of sleep for 24-hr, was markedly effective in inducing and maintaining both kinds of sleep. Prostaglandin D2 (0.36 nmol) was more effective in enhancing sleep at the later period of the infusion period. Uridine (10 pmol) caused a mild but long-lasting increase in sleep, especially in paradoxical sleep. Thus, each substance exhibited compound-specific sleep-modulating properties.

Full text

PDF
6240

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Borbély A. A. A two process model of sleep regulation. Hum Neurobiol. 1982;1(3):195–204. [PubMed] [Google Scholar]
  2. Constantinidis J., Bouras C., Guntern R., Taban C. H., Tissot R. Delta sleep-inducing peptide in the rat brain: an immunohistological microscopic study. Neuropsychobiology. 1983;10(2-3):94–100. doi: 10.1159/000117992. [DOI] [PubMed] [Google Scholar]
  3. Honda K., Ichikawa H., Inoué S. [Special rat cages for the assay of the sleep substance (author's transl)]. Tokyo Ika Shika Daigaku Iyo Kizai Kenkyusho Hokoku. 1974;8:149–152. [PubMed] [Google Scholar]
  4. Honda K., Inoue S. [Effects of sleep-promoting substance on sleep-waking patterns of male rats (author's transl)]. Tokyo Ika Shika Daigaku Iyo Kizai Kenkyusho Hokoku. 1981;15:115–123. [PubMed] [Google Scholar]
  5. Honda K., Komoda Y., Nishida S., Nagasaki H., Higashi A., Uchizono K., Inoué S. Uridine as an active component of sleep-promoting substance: its effects on nocturnal sleep in rats. Neurosci Res. 1984 Aug;1(4):243–252. doi: 10.1016/s0168-0102(84)80003-6. [DOI] [PubMed] [Google Scholar]
  6. Inoué S. [Sleep substances: their roles and evolution]. Seikagaku. 1983 Jul;55(7):445–460. [PubMed] [Google Scholar]
  7. Krueger J. M., Bacsik J., García-Arrarás J. Sleep-promoting material from human urine and its relation to factor S from brain. Am J Physiol. 1980 Feb;238(2):E116–E123. doi: 10.1152/ajpendo.1980.238.2.E116. [DOI] [PubMed] [Google Scholar]
  8. Krueger J. M., Pappenheimer J. R., Karnovsky M. L. Sleep-promoting effects of muramyl peptides. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6102–6106. doi: 10.1073/pnas.79.19.6102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Krueger J. M., Pappenheimer J. R., Karnovsky M. L. The composition of sleep-promoting factor isolated from human urine. J Biol Chem. 1982 Feb 25;257(4):1664–1669. [PubMed] [Google Scholar]
  10. Normanton J. R., Gent J. P. Comparison of the effects of two 'sleep' peptides, delta sleep-inducing peptide and arginine-vasotocin, on single neurons in the rat and rabbit brain stem. Neuroscience. 1983 Jan;8(1):107–114. doi: 10.1016/0306-4522(83)90029-5. [DOI] [PubMed] [Google Scholar]
  11. Pappenheimer J. R., Koski G., Fencl V., Karnovsky M. L., Krueger J. Extraction of sleep-promoting factor S from cerebrospinal fluid and from brains of sleep-deprived animals. J Neurophysiol. 1975 Nov;38(6):1299–1311. doi: 10.1152/jn.1975.38.6.1299. [DOI] [PubMed] [Google Scholar]
  12. Pappenheimer J. R., Miller T. B., Goodrich C. A. Sleep-promoting effects of cerebrospinal fluid from sleep-deprived goats. Proc Natl Acad Sci U S A. 1967 Aug;58(2):513–517. doi: 10.1073/pnas.58.2.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Schoenenberger G. A., Maier P. F., Tobler J. H., Monnier M. A naturally occurring delta-EEG enhancing nonapeptide in rabbits. X. Final isolation, characterization and activity test. Pflugers Arch. 1977 Jun 8;369(2):99–109. doi: 10.1007/BF00591565. [DOI] [PubMed] [Google Scholar]
  14. Ueno R., Honda K., Inoué S., Hayaishi O. Prostaglandin D2, a cerebral sleep-inducing substance in rats. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1735–1737. doi: 10.1073/pnas.80.6.1735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ueno R., Ishikawa Y., Nakayama T., Hayaishi O. Prostaglandin D2 induces sleep when microinjected into the preoptic area of conscious rats. Biochem Biophys Res Commun. 1982 Nov 30;109(2):576–582. doi: 10.1016/0006-291x(82)91760-0. [DOI] [PubMed] [Google Scholar]
  16. Ueno R., Narumiya S., Ogorochi T., Nakayama T., Ishikawa Y., Hayaishi O. Role of prostaglandin D2 in the hypothermia of rats caused by bacterial lipopolysaccharide. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6093–6097. doi: 10.1073/pnas.79.19.6093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Yamashita A., Watanabe Y., Hayaishi O. Autoradiographic localization of a binding protein(s) specific for prostaglandin D2 in rat brain. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6114–6118. doi: 10.1073/pnas.80.19.6114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Yehuda S., Kastin A. J., Coy D. H. Thermoregulatory and locomotor effects of DSIP: paradoxical interaction with d-amphetamine. Pharmacol Biochem Behav. 1980 Dec;13(6):895–900. doi: 10.1016/0091-3057(80)90225-7. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES