Skip to main content

Advertisement

SpringerLink
Log in

The serotonergic system may be involved in the sleep-inducing action of oleamide in rats

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

The mechanism underlying the sleep-inducing effect of oleamide, an endogenous fatty acid amide, was studied in rats. Animals implanted with cerebrocortical and dorsal neck muscle electrodes were monitored continuously by electroencephalograph (EEG) and electromyograph (EMG) for 4 h after i.p. or s.c. injection of drugs. Oleamide induced a dose-dependent increase in slow-wave sleep (SWS), a decrease in wakefulness (W) and sleep latency, but had no effect on rapid-eye-movement sleep (REMS). The oleamide-induced increase in SWS was prevented by 5-HT reuptake inhibitors such as fluoxetine or fenfluramine and by agonists at 5-HT1A receptors such as buspirone or 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT). Moreover, the selective 5-HT1A receptor antagonist WAY100635 markedly antagonized the suppression of the oleamide-induced increase in SWS by 8-OH-DPAT. These data provide the first behavioural evidence that the serotonergic system may be involved in the sleep-inducing action of oleamide in rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Basile AS, Hanus L, Mendelson WB (1999) Characterization of the hypnotic properties of oleamide. Neuroreport 10:947–951

    CAS  PubMed  Google Scholar 

  • Boger DL, Henriksen SJ, Cravatt BF (1998a) Oleamide: an endogenous sleep-inducing lipid and prototypical member of a new class of biological signaling molecules. Curr Pharm Des 4: 303–314

    CAS  PubMed  Google Scholar 

  • Boger DL, Patterson JE, Jin Q (1998b) Structural requirements for 5-HT2A and 5-HT1A serotonin receptor potentiation by the biological active lipid oleamide. Proc Natl Acad Sci USA 95:4102–4107

    Article  CAS  PubMed  Google Scholar 

  • Cape EG, Jones BE (1998) Differential modulation of high frequency gamma electroencephalogram activity and sleep-wake state by noradrenaline and serotonin microinjections into the region of cholinergic basalis neurons. J Neurosci 18:2653–2666

    CAS  PubMed  Google Scholar 

  • Cheer JF, Cadogan AK, Marsden CA, Fone KC, Kendall DA(1999) Modification of 5-HT2 receptor mediated behaviour in the rat by oleamide and the role of cannabinoid receptor. Neurophamarcology 38:533–541

    Article  CAS  Google Scholar 

  • Coyne L, Lees G, Nicholson RA, Zheng J, Neufield KD (2002) The sleep hormone oleamide modulates inhibitory ionotropic receptors in mammalian CNS in vitro. Br J Pharmacol 135:1977–1987

    CAS  PubMed  Google Scholar 

  • Cravatt BF, Prospero-Garcia O, Siuzdak G, Gilula NB, Henriksen SJ, Boger DL, Lerner RA (1995) Chemical characterization of a family of brain lipids that induce sleep. Science 268:1506–1509

    CAS  PubMed  Google Scholar 

  • Cravatt BF, Giang DK, Mayfield SP, Boger DL, Lerner RA, Gilula NB (1996) Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 384:83–87

    CAS  PubMed  Google Scholar 

  • De Montigny C, Blier P (1984) Effects of antidepressant treatments on 5-HT neurotransmission: electrophysiological and clinical studies. Adv Biochem Psychopharmacol 39:223–239

    PubMed  Google Scholar 

  • Fedorova I, Hashimoto A, Fecik RA, Hedrick MP, Hanus LO, Boger DL, Rice KC, Basile AS (2001) Behavioral evidence for the interaction of oleamide with multiple neurotransmitter systems. J Pharmacol Exp Ther 299:332–342

    PubMed  Google Scholar 

  • Fornal C, Radulovacki M (1983a) Sleep suppressant action of fenfluramine in rats: Relation to postsynaptic serotonergic stimulation. J Pharmacol Exp Ther 225:667–674

    CAS  PubMed  Google Scholar 

  • Fornal C, Radulovacki M (1983b) Sleep suppressant action of fenfluramine in rats: evidence against the involvement of presynaptic serotonergic mechanism. J Pharmacol Exp Ther 225:675–681

    CAS  PubMed  Google Scholar 

  • Gao B, Duncan WC Jr, Wehr TA (1992) Fluoxetine decreases brain temperature and REM sleep in Syrian hamsters. Psychopharmacology 106:321–329

    CAS  PubMed  Google Scholar 

  • Hedlund PB, Carson MJ, Sutcliffe JG, Thomas EAl (1999) Allosteric regulation by oleamide of the binding properties of 5-hydroxytryptamine7 receptors. Biochem Pharmacol 58: 1807–1813

    Article  CAS  PubMed  Google Scholar 

  • Huidobro-Toro JP, Harris RA (1996) Brain lipids that induce sleep are novel modulators of 5-HT receptors. Proc Natl Acad Sci USA 93:8078–8082

    Article  CAS  PubMed  Google Scholar 

  • Huitron-Resendiz S, Gombart L, Cravatt BF, Henriksen SJ (2001) Effect of oleamide on sleep and its relationship to blood pressure, body temperature, and locomotor activity in rats. Exp Neurol 172:235–243

    Article  CAS  PubMed  Google Scholar 

  • Hyttel J (1994) Pharmacological characterization of the selective serotonin reuptake inhibitors (SSRI’s). Int Clin Psychopharmacol 9:19–26

    Google Scholar 

  • Laposky AD, Homanics GE, Basile A, Mendelson WB (2001) Deletion of the GABA(A) receptor beta 3 subunit eliminates the hypnotic actions of oleamide in mice. Neuroreport 12:4143–4147

    CAS  PubMed  Google Scholar 

  • Lees G, Edwards MD, Hassoni AA, Ganellin CR, Galanakis D (1998) Modulation of GABAA receptors and inhibitory synaptic currents by the endogenous CNS sleep regulator cis-9,10-octadecenoamide (cOA). Br J Pharmacol 124:873–882

    CAS  PubMed  Google Scholar 

  • Lerman JA, Kaitin KI, Dement WC, Peroutka SJ (1986) The effects of buspirone on sleep in the rat. Neurosci Lett 72:64–68

    Article  CAS  PubMed  Google Scholar 

  • Mechoulam R, Fride E, Hanus L, Sheskin T, Bisogno T, Di Marzo V, Bayewitch M, Vogel Z (1997) Anandamide may mediate sleep induction. Nature 389:25–26

    CAS  PubMed  Google Scholar 

  • Mendelson WB, Basile AS (1999) The hypnotic actions of oleamide are blocked by a cannabinoid receptor antagonist. Neuroreport 10:3237–3239

    CAS  PubMed  Google Scholar 

  • Mendelson WB, Basile AS (2000) Synergistic interaction of the hypnotic effects of oleamide and triazolam (abstract). Sleep 23 (Suppl. 2):A162

  • Mistlberger RE, Bergamnn BM, Waldenar W, Rechtschaffen A (1983) Recovery sleep following sleep deprivation in intact and suprachiastmatic nuclei-lesioned rats. Sleep 6:217–233

    CAS  PubMed  Google Scholar 

  • Monti JM, Jantos H (1992) Dose-dependent effects of the 5-HT1A receptor agonist 8-OH-DPAT on sleep and wakefulness in the rat. J Sleep Res 1:169–175

    PubMed  Google Scholar 

  • Monti JM, Jantos H (1994) Stereoselective antagonism by the pindolol enantiomers of 8-OH-DPAT-induced changes of sleep and wakefulness Neuropharmacology 33:705–708

    Google Scholar 

  • Monti JM, Jantos H, Silveira R, Reyes-Parada M, Scorza C (1995) Sleep and waking in 5,7-DHT-lesioned or (−)-pindolol-pretreated rats after administration of buspirone, ipsapirone, or gepirone. Pharmacol Biochem Behav 52:305–312

    Article  CAS  PubMed  Google Scholar 

  • Nicholson AN, Pascoe PA (1988) Studies on the modulation of the sleep-wakefulness continuum in man by fluoxetine, a 5-HT uptake inhibitor. Neuropharmacology 27:597–602

    Article  CAS  PubMed  Google Scholar 

  • Obal F Jr, Tobler I, Borbley AA (1983) Effect of ambient temperature on 24 h sleep-wake cycle in normal and caspsaician treated rats. Physiol Behav 30:425–430

    Article  PubMed  Google Scholar 

  • Pastel RH, Fernstrom JD (1987) Short-term effects of fluoxetine and trifluoromethylphenylpiperazine on EEG in the rat. Brain Res 436:92–102

    Article  CAS  PubMed  Google Scholar 

  • Portas CM, Bjorvatn B, Ursin R (2000) Serotonin and the sleep/wake cycle: special emphasis on microdialysis studies. Prog Neurobiol 60:13–35

    CAS  PubMed  Google Scholar 

  • Sakai K, Crochet S (2001) Differentiation of presumed serotonergic dorsal raphe neurons in relation to behavior and wake-sleep states. Neuroscience 104:1141–1155

    Article  CAS  PubMed  Google Scholar 

  • Sorensen E, Gronli J, Bjorvatn B, Ursin R (2001) The selective 5-HT1A receptor antagonist p-MPPI antagonizes sleep-waking and behavioral effects of 8-OH-DPAT in rats. Behav Brain Res 121:181–187

    Article  CAS  PubMed  Google Scholar 

  • Thomas EA, Carson MJ, Neal MJ, Sutcliffe JG (1997) Unique allosteric regulation of 5-HT receptor-mediated signal transduction by oleamide. Proc Natl Acad Sci USA 94: 14115–14119

    Article  PubMed  Google Scholar 

  • Thomas EA, Carson MJ, Sutcliffe JG (1998) Oleamide-induced modulation of 5-hydroxytryptamine receptor-mediated signaling. Ann NY Acad Sci 861:183–189

    CAS  PubMed  Google Scholar 

  • Thomas TC, Kumar VM (2000) Effect of ambient temperature on sleep-wakefulness in normal and medial preoptic are lesioned rats. Sleep Res Online 3:141–145

    CAS  PubMed  Google Scholar 

  • Verdon B, Zheng J, Nicholson RA, Ganelli CR, Lees G (2000) Stereoselective modulatory actions of oleamide on GABAA receptors and voltage-gated Na+ channels in vitro: a putative endogenous ligand for depressant drug site in CNS. Br J Pharmacol 129:283–290

    CAS  PubMed  Google Scholar 

  • Yang JY, Wu CF, Song HR (1999) Studies on the sedative and hypnotic effects of oleamide in mice. Arzneim-Forsch/Drug Res 49:663–667

    Google Scholar 

Download references

Acknowledgements

This project is partially supported by Liaoning Nature Science Foundation.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, P.R. China

    Jing-Yu Yang, Chun-Fu Wu, Fang Wang & Wen-Jun Pan

  2. Department of Organic Chemistry, Shenyang Pharmaceutical University, 110016, Shenyang, P.R. China

    Hong-Rui Song & Yu-Ling Wang

Authors
  1. Jing-Yu Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chun-Fu Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hong-Rui Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wen-Jun Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu-Ling Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chun-Fu Wu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, JY., Wu, CF., Wang, F. et al. The serotonergic system may be involved in the sleep-inducing action of oleamide in rats. Naunyn-Schmiedeberg's Arch Pharmacol 368, 457–462 (2003). https://doi.org/10.1007/s00210-003-0843-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-003-0843-z

Keywords

Search

Navigation