Elsevier

NeuroImage

Volume 30, Issue 2, 1 April 2006, Pages 341-348
NeuroImage

Increased serotonin receptor availability in human sleep: Evidence from an [18F]MPPF PET study in narcolepsy

https://doi.org/10.1016/j.neuroimage.2005.09.052Get rights and content

Abstract

Data from animal studies suggest that serotonin release promotes wakefulness and suppresses REM sleep, but there are dangers in extrapolating these findings to humans. Binding of the radioligand [18F]MPPF to 5HT1A receptors is sensitive to levels of endogenous serotonin. In this study, we aimed to demonstrate changes in serotonin receptor availability in the human brain in wakefulness and sleep using [18F]MPPF and positron emission tomography. 14 subjects with narcolepsy cataplexy underwent [18F]MPPF PET scans in wakefulness and in sleep. Subjects who used the stimulant methylphenidate took their normal medication for the wake scan but omitted it prior to the sleep scan. The change in binding potential (BP) between the sleep and wake scans was examined using paired t test. Methylphenidate is thought to have little or no effect on serotonergic neurotransmission, and in order to confirm the absence of an effect on [18F]MPPF binding, a concurrent study was performed using a β-microprobe technique to examine the effect of methylphenidate administration on [18F]MPPF binding in Sprague–Dawley rats. The human study showed a significant increase in [18F]MPPF binding in sleep compared to wakefulness in the whole brain and all regions of interest examined (temporal cortex, mesial temporal region and cingulate cortex). The β-microprobe study confirmed that methylphenidate administration had no effect on [18F]MPPF binding. These findings indicate that serotonin receptor availability is increased in sleep compared to wakefulness in narcoleptic humans.

Section snippets

Subjects

One of the problems faced by functional neuroimaging studies of human sleep is the lack of predictability with which spontaneous sleep occurs. We chose to study patients with narcolepsy as a way of circumventing this problem. Fourteen subjects with a diagnosis of narcolepsy (12 females, 2 males; mean age ± standard deviation: 52 years ± 14; age range: 26–67 years) were studied. The clinical features of the subjects are described in Table 1. The following inclusion criteria were applied: age

Part 1: human study

Of the 14 subjects studied, 7 slept for greater than 75% of the study (‘Good sleepers’) and 7 slept for less than 75% of the scan time (‘Poor sleepers’).

Discussion

In this study, we have demonstrated an increase in [18F ]MPPF binding in sleep, indicating increased 5HT1A receptor availability in sleep compared to wakefulness. To our knowledge, this is the first time such changes have been demonstrated in the living human brain.

Acknowledgments

We thank the technicians in the Department of Neurology and the Centre for PET for making this work possible, and John Sachinidis and Graeme O'Keefe their for technical support during the study. We are grateful to NODSS and all volunteers for their participation. This work was supported by grants from the NHMRC, the French–Australian Science and Technology Program and the Brockoff foundation.

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