Novel biochemical manipulation of brain serotonin reveals a role of serotonin in the circadian rhythm of sleep-wake cycles

Eiko Nakamaru-Ogiso*, Hiroyuki Miyamoto, Kozo Hamada, Koji Tsukada, Katsuji Takai

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Serotonin (5-HT) neurons have been implicated in the modulation of many physiological functions, including mood regulation, feeding, and sleep. Impaired or altered 5-HT neurotransmission appears to be involved in depression and anxiety symptoms, as well as in sleep disorders. To investigate brain 5-HT functions in sleep, we induced 5-HT deficiency through acute tryptophan depletion in rats by intraperitoneally injecting a tryptophan-degrading enzyme called tryptophan side chain oxidase I (TSOI). After the administration of TSOI (20 units), plasma tryptophan levels selectively decreased to 1-2% of those of controls within 2h, remained under 1% for 12-24h, and then recovered between 72 and 96h. Following plasma tryptophan levels, brain 5-HT levels decreased to ~30% of the control level after 6h, remained at this low level for 20-30h, and returned to normal after 72h. In contrast, brain norepinephreine and dopamine levels remained unchanged. After TSOI injection, the circadian rhythms of the sleep-wake cycle and locomotive activity were lost and broken into minute(s) ultradian alternations. The hourly slow-wave sleep (SWS) time significantly increased at night, but decreased during the day, whereas rapid eye movement sleep was significantly reduced during the day. However, daily total (cumulative) SWS time was retained at the normal level. As brain 5-HT levels gradually recovered 48h after TSOI injection, the circadian rhythms of sleep-wake cycles and locomotive activity returned to normal. Our results suggest that 5-HT with a rapid turnover rate plays an important role in the circadian rhythm of sleep-wake cycles.

Original languageEnglish
Pages (from-to)1762-1770
Number of pages9
JournalEuropean Journal of Neuroscience
Volume35
Issue number11
DOIs
Publication statusPublished - Jun 2012
Externally publishedYes

Keywords

  • Animal model
  • Circadian rhythm
  • Depression
  • Serotonin
  • Sleep
  • Tryptophan depletion

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