Sleep Stage Transitions in Healthy Humans Altered by Central Monoaminergic Antagonist

 

 Buy Article Permissions and Reprints

Summary

Objectives: Sleep stage transitions constitute one of the key components of the dynamical aspect of sleep. However, neural mechanisms of sleep stage transitions have not, to date, been fully elucidated. We investigate the effects of administrating risperi-done, a central serotonergic and dopaminergic antagonist, on sleep stage transitions inhumans, and also on ultradian rapid-eye-movement (REM) sleep rhythms.

Methods: Ten healthy young male volunteers (age: 22 ± 3.7 years) participated in this study. The subjects spent three nights in a sleep laboratory. The first was the adaptation night, and the second was the baseline night. On the third night, the subjects received risperidone (1 mg tablet) 30 min before the polysomnography recording. We measured and investigated transition probabilities between waking, REM and non-REM (stages I–IV) sleep stages.

Results: We found that the probability of transition from stage II to stage III was significantly greater for the risperidone night than for the baseline night. We also found that risperidone administration prolonged REM-onset intervals, when compared to the baseline night.

Conclusions: We demonstrate that central serotonergic and /or dopaminergic neural transmissions are involved in the regulation of sleep stage transitions from light (stage II) to deep (stage III) sleep, and also in determining ultradian REM sleep rhythms.

• References

• 1 Hobson JA, Lydic R, Baghdoyan HA. Evolving concepts of sleep cycle generation: from brain centers to neuronal populations. Behav Brain Sci 1986; 9: 371-448.
  CrossrefPubMedGoogle Scholar
• 2 Saper CB, Chou TC, Scammell TE. The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci 2001; 24: 726-731.
  CrossrefPubMedGoogle Scholar
• 3 Pace-Schott EF, Hobson JA. The neurobiology of sleep: genetics, cellular physiology and subcortical networks. Nat Rev Neurosci 2002; 3: 591-605.
  CrossrefPubMedGoogle Scholar
• 4 Pace-Schott EF, Hobson JA. Basic mechanisms of sleep: new evidence on the neuroanatomy and neuromodulation of the NREM-REM cycle. In: Kenneth LD, Dennis C, Joseph TC, Charles N. editors. Neuropsychopharmacology: the fifth generation of progress. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002. pp 1859-1877.
  Google Scholar
• 5 Jones BE. Paradoxical REM sleep promoting and permitting neuronal networks. Arch Ital Biol 2004; 142: 379-396.
  PubMedGoogle Scholar
• 6 Luppi PH. et al. Brainstem structures responsible for paradoxical sleep onset and maintenance. Arch Ital Biol 2004; 142: 379-396.
  PubMedGoogle Scholar
• 7 Rechtschaffen A, Kales A. A manual of standardized terminology, techniques and scoring system for sleep states of human subjects. Washington, DC: US Government Printing Office; 1968
  Google Scholar
• 8 Lo CC. et al. Dynamics of sleep-wake transitions during sleep. Europhys Lett 2002; 57: 625-631.
  CrossrefPubMedGoogle Scholar
• 9 Lo CC. et al. Common scale-invariant patterns of sleep-wake transitions across mammalian species. Proc Natl Acad Sci USA 2004; 101: 17545-17548.
  CrossrefPubMedGoogle Scholar
• 10 Comte JC, Ravassard P, Salin PA. Sleep dynamics: a self-organized critical system. Phys Rev E Stat Nonlin Soft Matter Phys 2006; 73: 056127.
  CrossrefPubMedGoogle Scholar
• 11 Kishi A. et al. Dynamics of sleep stage transitions in healthy humans and patients with chronic fatigue syndrome. Am J Physiol Regul Integr Comp Physiol 2008; 294: 1980-1987.
  CrossrefPubMedGoogle Scholar
• 12 Carskadon MA, Dement WC. Normal human sleep overview. In: Kryger MH, Roth T, Dement WC. (eds). Principles and practice of sleep medicine. 4th ed. Philadelphia, PA: Elsevier Saunders; 2005. pp 13-23.
  CrossrefGoogle Scholar
• 13 Phillips AJK, Robinson PA. A quantitative model of sleep-wake dynamics based on the physiology of the brainstem ascending arousal system. J Biol Rhythms 2007; 22: 167-179.
  CrossrefPubMedGoogle Scholar
• 14 Matsumoto M. et al. Effect of risperidone on polysomnography in healthy subjects. Sleep Biol Rhythms 2007; 5: 146-148.
  CrossrefPubMedGoogle Scholar
• 15 McCarley RW, Hobson JA. Neuronal excitability modulation over the sleep cycle: a structural and mathematical model. Science 1975; 189: 58-60.
  CrossrefPubMedGoogle Scholar
• 16 Sitaram N, Moore AM, Gillin JC. Experimental acceleration and slowing of REM sleep ultradian rhythm by cholinergic agonist and antagonist. Nature 1978; 274: 490-492.
  CrossrefPubMedGoogle Scholar
• 17 Benington JH, Heller HC. Monoaminergic and cholinergic modulation of REM-sleep timing in rats. Brain Res 1995; 681: 141-146.
  CrossrefPubMedGoogle Scholar
• 18 Feinberg I. Changes in sleep cycle patterns with age. J Psychiat Res 1974; 10: 283-306.
  CrossrefPubMedGoogle Scholar
• 19 Moses J. et al. Rapid eye movement cycle is a sleep-dependent rhythm. Nature 1977; 265: 360-361.
  CrossrefPubMedGoogle Scholar
• 20 Sharpley AI. et al.. Risperidone augmentation decreases rapid eye movement sleep and decreases wake in treatment-resistant depressed patients. J Clin Psychiatry 2003; 64: 192-196.
  CrossrefPubMedGoogle Scholar
• 21 Giménes S. et al. Effects of olanzapine, risperidone and haloperidol on sleep after single oral morning dose in healthy volunteers. Psychopharmacology 2007; 190: 507-516.
  CrossrefPubMedGoogle Scholar
• 22 Yamashita H. et al. Effect of risperidone on sleep in schizophrenia: a comparison with haloperidol. Psychiat Res 2002; 109: 137-142.
  CrossrefPubMedGoogle Scholar