Promotion of non-rapid eye movement sleep in mice after oral administration of ornithine


We examined the effects of ornithine on the sleep-wake cycle by monitoring the electroencephalo-gram, electromyogram, and locomotor activity of freely moving mice after oral administration of it at lights-off time (18:00). Ornithine (1.0 and 3.0 g/kg of body weight) increased the amount of non-rapid eye movement (non-REM, NREM) sleep for 2 h after its administration, with a peak at 60 min post administration, to 164% and 198%, respectively, of that of the vehicle-administered mice, without changing the amount of REM sleep. The administration of ornithine at a lower dose (0.3 g/kg of body weight) did not increase the amount of NREM sleep compared with the vehicle administration. Ornithine did not affect the power spectrum density of NREM sleep but increased the number of episodes of wakefulness and NREM sleep and that of transitions between wakefulness and NREM sleep, and decreased the mean duration of wake episodes in a dose-dependent manner for 2 h after the oral administration. These results indicate that ornithine increased the amount of NREM sleep without reducing the power spectrum density of NREM sleep.

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  1. 1

    Eisenberg DM, Davis RB, Ettner SL et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 1998; 280: 1569–75.

    CAS  Article  PubMed  Google Scholar 

  2. 2

    Gyllenhaal C, Merritt SL, Peterson SD et al. Efficacy and safety of herbal stimulants and sedatives in sleep disorders. Sleep Med. Rev. 2000; 4: 229–51.

    Article  PubMed  Google Scholar 

  3. 3

    Meoli AL, Rosen C, Kristo D et al. Oral nonprescription treatment for insomnia: an evaluation of products with limited evidence. J. Clin. Sleep Med. 2005; 1: 173–87.

    Google Scholar 

  4. 4

    Tokunaga S, Takeda Y, Niimoto T et al. Effect of valerian extract preparation (BIM) on the sleep-wake in rats. Biol. Pharm. Bull. 2007 (Feb); 30 (2): 363–6.

    CAS  Article  PubMed  Google Scholar 

  5. 5

    Makino Y, Kondo S, Nishimura Y et al. Hastatoside and verbenalin are sleep-promoting components in verbena officinalis. Sleep Biol. Rhythms 2009; 7: 211–17.

    Article  Google Scholar 

  6. 6

    Masaki M, Aritake K, Tanaka H et al. Crocin promotes non-rapid eye movement sleep in mice. Mol. Nutr. Food Res. 2011. doi:10.1002/mnfr.201100181.

    Google Scholar 

  7. 7

    Ozeki M, Juneja LR, Shirakawa S. The effects of theanine on sleep with physiological evaluation using actigraph. J. Physiol. Anthropol. 2004; 23: 58.

    Google Scholar 

  8. 8

    Inagawa K, Hiraoka T, Kohda T et al. Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep Biol. Rhythms 2006; 4: 75–7.

    Article  Google Scholar 

  9. 9

    Sugino T, Shirai T, Kajimoto Y et al. L-Ornithine supple-mentation attenuates physical fatigue in healthy volun-teers by modulating lipid and amino acid metabolism. Nutr. Res. 2008; 28: 738–43.

    CAS  Article  PubMed  Google Scholar 

  10. 10

    Hong ZY, Huang ZL, Qu WM et al. An adenosine A2A receptor agonist induces sleep by increasing GABA release in the tuberomammillary nucleus to inhibit histaminergic systems in rats. J. Neurochem. 2005; 92: 1542–49.

    CAS  Article  PubMed  Google Scholar 

  11. 11

    Huang ZL, Mochizuki T, Qu WM et al. Altered sleep-wake characteristics and lack of arousal response to H3 receptor antagonist in histamine H1 receptor knockout mice. Proc. Natl. Acad. Sci. USA 2006; 103: 4687–92.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12

    Kohtoh S, Taguchi Y, Matsumoto N et al. Algorithm for sleep scoring in experimental animals based on fast Fourier transform power spectrum analysis of the electroencephalogram. Sleep Biol. Rhythms 2008; 6: 163–71.

    Article  Google Scholar 

  13. 13

    Huang ZL, Qu WM, Eguchi N et al. Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nat. Neurosci. 2005; 8: 858–9.

    CAS  Article  PubMed  Google Scholar 

  14. 14

    Qiu MH, Qu WM, Xu XH et al. D(1)/D(2) receptor-targeting L-stepholidine, an active ingredient of the Chinese herb Stephonia, induces non-rapid eye move-ment sleep in mice. Pharmacol. Biochem. Behav. 2009; 94: 16–23.

    CAS  Article  PubMed  Google Scholar 

  15. 15

    Hambrecht-Wiedbusch VS, Gauthier EA, Baghdoyan HA et al. Benzodiazepine receptor agonists cause drug-specific and state-specific alterations in EEG power and acetylcholine release in rat pontine reticular formation. Sleep 2010; 33: 909–18.

    PubMed  PubMed Central  Google Scholar 

  16. 16

    Bucci L, Hickson JF, Pivarnik JM et al. Ornithine ingestion and growth hormone release in bodybuilders. Nutr. Res. 1990; 10: 239–45.

    CAS  Article  Google Scholar 

  17. 17

    Davidson MB. Effect of growth hormone on carbohy-drate and lipid metabolism. Endocr. Rev. 1987; 8: 115–31.

    CAS  Article  PubMed  Google Scholar 

  18. 18

    Philipp L, Brett L, Peiyuan L et al. Novel role for arginase in cell survival, regeneration, and translation in the central nervous system. J. Nutr. 2004; 134: 2812–17.

    Google Scholar 

  19. 19

    Hamasu K, Shigemi K, Tsuneyoshi Y et al. Intracere-broventricular injection of L-proline and D-proline induces sedative and hypnotic effects by different mechanisms under an acute stressful condition in chicks. Amino Acids 2010; 38: 57–64.

    CAS  Article  PubMed  Google Scholar 

  20. 20

    Yamane H, Tsuneyoshi Y, Denbow DM et al. N-Methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors involved in the induction of sedative effects under an acute stress in neonatal chicks. Amino Acids 2009; 37: 733–9.

    CAS  Article  PubMed  Google Scholar 

  21. 21

    Suenaga R, Yamane H, Tomonaga S et al. Central L-arginine reduced stress responses are mediated by L-ornithine in neonatal chicks. Amino Acids 2008; 35: 107–13.

    CAS  Article  PubMed  Google Scholar 

  22. 22

    Kurauchi I, Shigemi K, Kabuki Y et al. Central L-ornithine, but not polyamines, induces a hypnotic effect in neonatal chicks under acute stress. Nutr. Neurosci. 2010; 13: 17–20.

    CAS  Article  PubMed  Google Scholar 

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Correspondence to Mr Ken Omori.

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Omori, K., Kagami, Y., Yokoyama, C. et al. Promotion of non-rapid eye movement sleep in mice after oral administration of ornithine. Sleep Biol. Rhythms 10, 38–45 (2012).

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  • electroencephalogram
  • mouse
  • non-rapid eye movement sleep
  • ornithine
  • power spectrum analysis
  • wakefulness