Present addresses: Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, PA 19104, USA.
Novel biochemical manipulation of brain serotonin reveals a role of serotonin in the circadian rhythm of sleep–wake cycles
Version of Record online: 24 MAY 2012
© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 35, Issue 11, pages 1762–1770, June 2012
How to Cite
Nakamaru-Ogiso, E., Miyamoto, H., Hamada, K., Tsukada, K. and Takai, K. (2012), Novel biochemical manipulation of brain serotonin reveals a role of serotonin in the circadian rhythm of sleep–wake cycles. European Journal of Neuroscience, 35: 1762–1770. doi: 10.1111/j.1460-9568.2012.08077.x
- Issue online: 5 JUN 2012
- Version of Record online: 24 MAY 2012
- Received 13 September 2011, revised 27 January 2012, accepted 13 February 2012
- animal model;
- circadian rhythm;
- tryptophan depletion
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 2 h, remained under 1% for 12–24 h, and then recovered between 72 and 96 h. Following plasma tryptophan levels, brain 5-HT levels decreased to ∼30% of the control level after 6 h, remained at this low level for 20–30 h, and returned to normal after 72 h. 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 48 h 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.