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

Summary & key facts

Researchers used an enzyme to sharply lower the building block for serotonin in rats and found that when brain serotonin fell, the animals lost their normal day-night sleep pattern. Sleep became broken into many short episodes. Deep sleep changed timing but the total amount over 24 hours stayed about the same. When serotonin levels went back up after a few days, the normal sleep rhythm returned. This suggests that fast-changing serotonin helps keep the sleep-wake cycle tied to day and night, but the study was done in rats so it does not prove the same thing happens in people.

Key facts:

• The team injected an enzyme that destroys tryptophan, the raw material the brain uses to make serotonin.
• Blood tryptophan fell to about 1 to 2 percent of normal within 2 hours and stayed extremely low for about 12 to 24 hours.
• Brain serotonin dropped to about 30 percent of its normal level after 6 hours and stayed low for about 20 to 30 hours.
• Other brain chemicals linked to arousal, like norepinephrine and dopamine, did not change.
• When serotonin was low, the rats lost their normal circadian rhythm of sleeping at night and being awake in the day and instead switched sleep and activity into many short, almost minute-long cycles.
• Nighttime deep sleep increased hour by hour but daytime deep sleep decreased, and dream sleep was reduced during the day, while the total amount of deep sleep across a full day stayed about the same.
• About three days after the enzyme injection, serotonin levels and normal day-night sleep patterns returned.
• Because this experiment was done in rats, the findings suggest a possible role for quickly changing serotonin in keeping sleep tied to day and night, but they do not directly prove the same effect in humans.

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 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.

Topics

Circadian rhythm and melatonin Neurotransmitter Receptor Influence on Behavior Sleep and Wakefulness Research

Categories

Cognitive Neuroscience Life Sciences Neuroscience

Tags

Amino acid Biochemistry Chemistry Circadian rhythm Computer science Dopamine Electroencephalography Endocrinology Internal medicine Medicine Neuroscience Operating system Psychology Receptor Serotonergic Serotonin Sleep (system call) Slow-wave sleep Tryptophan Tryptophan hydroxylase Ultradian rhythm

Conditions & symptoms

Anxiety Depression Sleep disorder Lack of energy or motivation Poor sleep Sadness or low mood