Skip to main content

Advertisement

Log in

The involvement of serotonin receptors in suanzaorentang-induced sleep alteration

  • Published:
Journal of Biomedical Science

Summary

Sedative-hypnotic medications, including benzodiazepines and non-benzodiazepines, are usually prescribed for the insomniac patients; however, the addiction, dependence and adverse effects of those medications have drawn much attention. In contrast, suanzaorentang, a traditional Chinese herb remedy, has been efficiently used for insomnia relief in China, although its mechanism remains unclear. This study was designed to further elucidate the underlying mechanism of suanzaorentang on sleep regulation. One ingredient of suanzaorentang, zizyphi spinosi semen, exhibits binding affinity for serotonin (5-hydroxytryptamine, 5-HT) receptors, 5-HT1A and 5-HT2, and for GABA receptors. Our previous results have implicated that GABAA receptors, but not GABAB, mediate suanzaorentang-induced sleep alteration. In current study we further elucidated the involvement of serotonin. We found that high dose of suanzaorentang (4 g/kg/2 ml) significantly increased non-rapid eye movement sleep (NREMS) when comparing to that obtained after administering starch placebo, although placebo at dose of 4 g/kg also enhanced NREMS comparing with that obtained from baseline recording. Rapid eye movement sleep (REMS) was not altered. Administration of either 5-HT1A antagonist (NAN-190), 5-HT2 antagonist (ketanserin) or 5-HT3 antagonist (3-(4-Allylpiperazin-1-yl)-2-quinoxalinecarbonitrile) blocked suanzaorentang-induced NREMS increase. These results implicate the hypnotic effect of suanzaorentang and its effects may be mediated through serotonergic activation, in addition to GABAergic system.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Partinen M. (1994). Epidemiology of sleep disorders, In: Kryger M.H., Roth T., Dement W.C. (Eds), Principles and Practice of Sleep Medicine. WB Saunders, Philadelphia, pp. 437–452

    Google Scholar 

  2. Chung K.F., Lee C.K.Y. (2002). Over-the-counter sleeping pills: a survey of use in Hong Kong and a review of their constituents. Gen. Hosp. Psychiatry 24: 430–435

    Article  PubMed  Google Scholar 

  3. Chen H.C., Hsieh M.T. (1985). Clinical trial of suanzaorentang in the treatment of insomnia. Clin. Therapeut. 7: 334–337

    CAS  Google Scholar 

  4. Chen H.C., Hsieh M.T., Shibuya T. (1986). Suanzaorentang versus diazepam: a controlled double-blind study in anxiety. Int. J. Clin. Pharmacol. Therapy Toxicol. 24: 646–650

    CAS  Google Scholar 

  5. Yi P.L., Tsai C.H., Chen Y.C., Chang F.C. (2007). Gamma-aminobutyric acid (GABA) receptor mediates suanzaorentang, a traditional Chinese herb remedy, induced sleep alteration. J. Biomed. Sci. 14: 285–297

    Article  PubMed  Google Scholar 

  6. Park J.H., Lee H.J., Koh S.M., Ban J.Y., Seong Y.H. (2004). Protection of NMDA-induced neuronal cell damage by methanol extract of Zizyphi Spinosi Semen in cultured rat cerebellar granule cells. J. Ethnopharmacol. 95: 39–45

    Article  PubMed  Google Scholar 

  7. Zheng H.Z., Dong A.H. and She J., (Eds) Modern Study of Traditional Chinese Medicine (in Chinese). Xue Yuan Press, Beijing, 1997

  8. Kanba S., Yamada K., Mizushima H., Murata T., Asai M. (1999). Use of herbal medicine for treating psychiatric disorders in Japan. In: Kanba S., Richelson E. (Eds), Herbal Medicines for Neuropsychiatric Diseases: Current Developments and Research. Brunner/Mazel, New York, pp. 3–14

    Google Scholar 

  9. Yu S.J., Tseng J. (1996). Fu-ling, a Chinese herbal drug, modulates cytokine secretion by human peripheral blood monocytes. Int. J. Immunopharmacol. 18: 37–44

    Article  PubMed  CAS  Google Scholar 

  10. Liao S.L., Kao T.K., Chen W.Y., Lin Y.S., Chen S.Y., Raung S.L., Wu C.W., Lu H.C., Chen C.J. (2004). Tetramethylpyrazine reduces ischemic brain injury in rats. Neurosci. Lett. 372: 40–45

    Article  PubMed  CAS  Google Scholar 

  11. Tsukamoto S., Wakana T., Koimaru K., Yoshida T., Sato M., Ohta T. (2005). 7-Hydroxy)3-(4-hydroxybenzyl) chroman and Broussonin B: neurotrophic compounds, isolated from Anemarrhena asphodeloides BUNGE, function as proteasome inhibitors. Biol. Pharm. Bull. 28: 1798–1800

    Article  PubMed  CAS  Google Scholar 

  12. Tsuda T., Kubota K., Yasuda K., Nishikawa S., Sugaya A., Sugaya E. (1986). Effects of Chinese herbal medicine ‹‹kanbaku-taiso-to’’ on transmembrane ionic currents and its local anesthetic action. J. Ethnopharmacol. 17: 257–261

    Article  PubMed  CAS  Google Scholar 

  13. Liao J.F., Jan Y.M., Huang S.Y., Wang H.H., Yu L.L., Chen C.F. (1995). Evaluation with receptor binding assay on the water extracts of ten CNS-active Chinese herbal drugs. Proc. Natl. Sci. Council ROC – Part B Life Sci. 19: 151–158

    CAS  Google Scholar 

  14. Jouvet M. (1999). Sleep and serotonin: an unfinished story. Neuropsychopharmacology 21: 24S–27S

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  16. Jouvet M. (1968). Insomnia and decrease of cerebral 5-hydroxytryptamine after destruction of the raphe system in the cat. Adv. Pharmacol. 6(Pt B): 265–279

    Article  PubMed  CAS  Google Scholar 

  17. Jouvet M. (1969). Biogenic amines and the states of sleep. Science 163: 32–41

    Article  PubMed  CAS  Google Scholar 

  18. Pujol J.F., Buguet A., Froment J.L., Jones B., Jouvet M. (1971). The central metabolism of serotonin in the cat during insomnia. A neurophysiological and biochemical study after administration of p-chlorophenylalanine or destruction of the raphe system. Brain Res. 29: 195–212

    Article  PubMed  CAS  Google Scholar 

  19. Monti J.M., Jantos H. (2004). Effects of the 5-HT1A receptor ligands flesinoxan and WAY 100635 given systemically or microinjected into the laterodorsal tegmental nucleus on REM sleep in the rat. Behav. Brain Res. 151: 159–166

    Article  PubMed  CAS  Google Scholar 

  20. Popa D., Lena C., Fabre V., Prenat C., Gingrich J., Escourrou P., Hamon M., Adrien J. (2005). Contribution of 5-HT2 receptor subtypes to sleep-wakefulness and respiratory control, and functional adaptations in knock-out mice lacking 5-HT2A receptors. J. Neurosci. 25: 11231–11238

    Article  PubMed  CAS  Google Scholar 

  21. Yi P.L., Tsai C.H., Lu M.K., Liu H.J., Chen Y.C., Chang F.C. (2007). Interleukin-1β mediates sleep alteration in rats with rotenone-induced parkinsonism. Sleep 30: 413–425

    PubMed  Google Scholar 

  22. Epstein A.M., Fitzsimons J.T., Rolls B.J. (1970). Drinking induced by injection of angiotensin into the brain of the rat. J. Physiol. 210: 457–474

    PubMed  CAS  Google Scholar 

  23. Chang F.-C., Opp M.R. (1998). Blockade of corticotropin releasing hormone receptors reduces spontaneous waking in the rat. Am. J. Physiol. 275: R793–R802

    PubMed  CAS  Google Scholar 

  24. Jorgensen H., Kjaer A., Warberg J., Knigge U. (2001) Differential effects of serotonin 5-HT1A receptor antagonists on the secretion of corticotropin and prolactin. Neuroendocrinology 73: 322–333

    Article  PubMed  CAS  Google Scholar 

  25. Engleman E.A., Murphy J.M., Zhou F.C., Aprison M.H., Hingtgen J.N. (1995) Operant response suppression induced with systemic administration of 5-hydroxytryptophan is centrally mediated. Pharmacol. Biochem. Behav. 52: 525–529

    Article  PubMed  CAS  Google Scholar 

  26. Weinger M.B., Chen D.Y., Lin T., Lau C., Koob G.F., Smith N.T. (1995). A role for CNS alpha-2 adrenergic receptors in opiate-induced muscle rigidity in the rat. Brain Res. 669: 10–18

    Article  PubMed  CAS  Google Scholar 

  27. Hansen M.K., Kapas L., Fang J., Krueger J.M. (1998). Cafeteria diet-induced sleep is blocked by subdiaphragmatic vagotomy in rats. Am. J. Physiol. 274: R168–R174

    PubMed  CAS  Google Scholar 

  28. Jenkins J.B., Omori T., Guan Z., Vgontzas A.N., Bixler E.O., Fang J. (2006). Sleep is increased in mice with obesity induced by high-fat food. Physiol. Behav. 87: 255–262

    Article  PubMed  CAS  Google Scholar 

  29. Vgontzas A.N., Papanicolaou D.A., Bixler E.O., Chrousos G.P. (1997). Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J. Clin. Endocrinol. Metab. 82: 1313–1316

    Article  PubMed  CAS  Google Scholar 

  30. Kubota T., Fang J., Guan Z., Brown R.A., Krueger J.M. (2001). Vagotomy attenuates tumor necrosis factor-alpha induced sleep and EEG delta-activity in rats. Am. J. Physiol. Regulat. Integr. Comp. Physiol. 280: R1213–R1220

    CAS  Google Scholar 

  31. McGinty D.J., Harper R.M. (1976). Dorsal raphe neurons: depression of firing during sleep in cats. Brain Res. 101: 569–575

    Article  PubMed  CAS  Google Scholar 

  32. Zhao X., Cui X.Y., Chu Q.P., Chen B.Q., Wang X.M., Lin Z.B., Li X.J., Ku B.S., Zhang Y.H. (2006). Potentiating effects of L-type Ca2+ channel blockers on pentobarbital-induced hypnosis are influenced by serotonergic system. J. Neural Transm. 113: 1395–1402

    Article  PubMed  CAS  Google Scholar 

  33. Guha M., Biswas S., Poddar M.K. (1988). Possible involvement of central cholinergic-serotonergic interaction in nature sleep. Methods Find Exp. Clin. Pharmacol. 10: 243-245

    PubMed  CAS  Google Scholar 

  34. Gao B., Duncan W.C. Jr., Wehr T.A. (1992). Fluoxetine decreases brain temperature and REM sleep in Syrian hamsters. Psychopharmacology 106: 321–329

    Article  PubMed  CAS  Google Scholar 

  35. Neckelmann D., Bjorkum A.A., Bjorvatn B., Ursin R. (1996). Sleep and EEG power spectrum effects of the 5-HT1A antagonist NAN-190 alone and in combination with citalopram. Behav. Brain Res. 75: 159–168

    Article  PubMed  CAS  Google Scholar 

  36. Depoortere H. (1988). Effects of 5-HT1A-agonists on the sleep-wakefulness cycle in rats. In: Koella W.P., Obal F., Schulz H., Visser P. (Eds), Sleep’86 Proceedings of the 8th European Congress on Sleep Research. Gustav-Fisher-Verlag, Stuttgart, pp. 346–348

    Google Scholar 

  37. Monti J.M., 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 

  38. Tissier M.H., Lainey E., Fattaccini C.-M., Hamon M., Adrien J. (1993) Effects of ipsapirone, a 5-HT1A agonist, on sleep/wakefulness cycles: probable post-synaptic action. J. Sleep Res. 2: 103–109

    Article  PubMed  Google Scholar 

  39. Dugovic C. (2001) Role of serotonin in sleep mechanisms. Rev. Neurol. 157: S16–S19

    PubMed  CAS  Google Scholar 

  40. Adrien J. (1995). The serotoninergic system and sleep-wakefulness regulation. In: Kales A. (Ed), The Pharmacology of Sleep. Springer-Verlag, Berlin, pp. 91–116

    Google Scholar 

  41. Siegel J.M. (2004). Hypocretin (orexin): role in normal behavior and neuropathology. Annu. Rev. Psychol. 55: 125–148

    Article  PubMed  Google Scholar 

  42. Lee M. and Jones B.E., Discharge of identified orexin neurons across the sleep-wake cycle. Neurosci. Abstr. 841.1, 2004

  43. Thakkar M.M., Ramesh V., Strecker R.E., McCarley R.W. (2001). Microdialysis perfusion of orexin-A in the basal forebrain increases wakefulness in freely behaving rats. Arch. Ital. Biol. 139: 313–328

    PubMed  CAS  Google Scholar 

  44. Bourgin P., Huitron-Resendiz S., Spier A.D., Fabre V., Morte B., Criado J.R., Sutcliffe J.G., Henriksen S.J., de Lecea L. (2000). Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons. J. Neurosci. 20: 7760–7765

    PubMed  CAS  Google Scholar 

  45. Chemelli R.M., Willie J.T., Sinton C.M., Elmquist J.K., Scammell T., Lee C., Richardson J.A., Williams S.C., Xiong Y., Kisanuki Y., Fitch T.E., Nakazato M., Hammer R.E., Saper C.B., Yanagisawa M. (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98: 437–451

    Article  PubMed  CAS  Google Scholar 

  46. Thannickal T.C., Moore R.Y., Nienhuis R., Ramanathan L., Gulyani S., Aldrich M., Cornford M., Siegel J.M. (2000). Reduced number of hypocretin neurons in human narcolepsy. Neuron 27: 469–474

    Article  PubMed  CAS  Google Scholar 

  47. Leander P., Vrang N., Moller M. (1998) Neuronal projections from the mesencephalic raphe nuclear complex to the suprachiasmatic nucleus and the deep pineal gland of the golden hamster (Mesocricetus auratus). J. Comp. Neurol. 399: 73–93

    Article  PubMed  CAS  Google Scholar 

  48. Muraki Y., Yamanaka A., Tsujino N., Kilduff T.S., Goto K., Sakurai T. (2004). Serotonergic regulation of the orexin/hypocretin neurons through the 5-HT1A receptor. J. Neurosci. 24: 7159–7166

    Article  PubMed  CAS  Google Scholar 

  49. Imeri L., Mancia M., Opp M.R. (1999). Blockade of 5-hydroxytryptamine (serotonin)-2 receptors alters interleukin-1-induced changes in rat sleep. Neuroscience 92: 745–749

    Article  PubMed  CAS  Google Scholar 

  50. Ponzoni A., Monti J.M., Jantos H. (1993). The effects of selective activation of the 5-HT3 receptor with m-chlorophenylbiguanide on sleep and wakefulness in the rat. Eur. J. Neurosci. 249: 259–264

    CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Science Council grant NSC95-2320-B-002-098-MY2.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fang-Chia Chang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yi, PL., Lin, CP., Tsai, CH. et al. The involvement of serotonin receptors in suanzaorentang-induced sleep alteration. J Biomed Sci 14, 829–840 (2007). https://doi.org/10.1007/s11373-007-9197-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11373-007-9197-8

Keywords

Navigation