Serotonergic hypothesis of sleepwalking

doi:10.1016/j.mehy.2004.06.013

Medical Hypotheses

Volume 64, Issue 1, 2005, Pages 28-32

https://doi.org/10.1016/j.mehy.2004.06.013 Get rights and content

Summary

Despite widespread prevalence of sleepwalking, its etiology and pathophysiology are not well understood. However, there is some evidence that sleepwalking can be precipitated by sleep-disordered breathing. A hypothesis is proposed that serotonergic system may be a link between sleep-disordered breathing and sleepwalking. Serotonergic neurons meet basic requirements for such a role because they are activated by hypercapnia, provide a tonic excitatory drive that gates afferent inputs to motoneurons, and the activity of serotonergic neurons can be dissociated from the level of arousal. This paper discusses also drug-induced somnambulism and co-occurrence of sleepwalking and other disorders such as migraine and febrile illness.

Section snippets

The characteristic of sleepwalking

Sleepwalking (somnambulism) is one of the most common parasomnias and refers to various complex motor behaviours, including walking, that are initiated during deep (stages 3–4) non-rapid-eye-movement (NREM) sleep. Some episodes may be limited to sitting up, fumbling, picking at bedclothes, and mumbling but usually sleepwalkers usually stand up and walk around quietly and aimlessly. Occasionally, they become agitated, with thrashing about, screaming, running, and aggressive behavior [1]. The

Etiology of sleepwalking

Despite widespread prevalence of sleepwalking, its etiology and pathophysiology are not well understood [2], [3]. To date, genetic, developmental, organic, and psychological factors have been proposed as causes of sleepwalking and somnambulism episodes can be triggered by fever, medication with some drugs, stress and major life events [4]. Recently, Bassetti et al. [1] proposed that sleepwalking could result from activation of thalamocingulate pathways and persisting deactivation of other

The role of serotonergic neurons in chemoreception

Cell bodies containing serotonin (5-hydroxytryptamine; 5-HT) are localized in two major groups in or near the brain stem raphe nuclei [7]. The rostral group, localized in the pons/mesencephalon, contains the dorsal (DRN) and the median (MRN) raphe nuclei whereas the caudal group, localized in the medulla, is comprised primarily of the nuclei raphe magnus, obscurus and pallidus (NRM, NRO and NRP, respectively). Medullary 5-HT neurons are located proximally within the vascular tree, close to

The role of serotonin in control of motor activity

According to Jacobs and Fornal [9], the primary role of brain serotonergic system is facilitation of gross motor movement. It has been shown, using various methods, that serotonin exerts facilitatory effects on motoneurons. In vivo application of 5-HT in the vicinity of spinal motoneurons or systemic injection of 5-HT precursors leads to an increase in motoneuronal excitability, increases tonic muscle electromyogram (EMG) activity and facilitates some spinal motor reflexes [10]. Large body of

The limited role of serotonin in arousal

Although the discharge rate of raphe 5-HT neurons is grossly correlated with level of arousal across the sleep-wakefulness cycle, it has also been shown that activity of serotonergic neurons modulating the motor system can be dissociated from the arousal. In cats with lesions of the dorsomedial pons, the activity of DRN 5-HT neurons was similar to that in normal cats during waking and NREM sleep and these pontine lesioned animals displayed normal waking behavior [11]. However, during REM sleep

The role of serotonin in pathophysiology of sleepwalking

We would like to put forward a hypothesis that serotonergic system may be a link between abnormal breathing and motor activity during sleep. The 5-HT neurons can play such a role because serotonin provides a tonic excitatory drive that gates afferent inputs to motoneurons, the activity of raphe neurons can be dissociated from the level of arousal, and raphe neurons are activated by hypercapnic acidosis. Normally, the responsiveness of 5-HT neurons to systemic CO₂ stimulation is greatly reduced

Conclusions

In summary, cerebral serotonergic system may play an important role in pathophysiology of sleepwalking. This hypothesis is supported by the fact that several factors known to precipitate episodes of sleepwalking activate serotonergic system. The higher prevalence of other sleep disorders, including night terrors and enuresis, in sleepwalkers suggest that sleepwalking may be a part of a more generalized sleep disturbance and can share a common pathophysiological substrate [35]. Therefore,

References (35)

C. Bassetti et al.
SPECT during sleepwalking
Lancet
(2000)
B.L. Jacobs et al.
Activity of medullary serotonergic neurons in freely moving animals
Brain Res. Rev.
(2002)
G.B. Richerson et al.
Chemosensitivity of serotonergic neurons in the rostral ventral medulla
Respir. Physiol.
(2001)
B.L. Jacobs et al.
Activity of serotonergic neurons in behaving animals
Neuropsychopharmacology
(1999)
M.E. Trulson et al.
Raphe unit activity during REM sleep in normal cats and in pontine lesioned cats displaying REM sleep without atonia
Brain Res.
(1981)
G.F. Steinfels et al.
Raphe unit activity in freely moving cats is altered by manipulations of central but not peripheral motor systems
Brain Res.
(1983)
T. Jolas et al.
Opioids suppress spontaneous and NMDA-induced inhibitory postsynaptic currents in the dorsal raphe nucleus of the rat in vitro
Brain Res.
(1997)
R. Liu et al.
Neurokinins activate local glutamatergic inputs to serotonergic neurons of the dorsal raphe nucleus
Neuropsychopharmacology
(2002)
T. Jolas et al.
Neurotensin and the serotonergic system
Prog. Neurobiol.
(1997)
J.A. Terron
Is the 5-HT₇ receptor involved in the pathogenesis and prophylactic treatment of migraine?
Eur J Pharmacol
(2002)

F. Espa et al.

Sleep architecture, slow wave activity, and sleep spindles in adult patients with sleepwalking and sleep terrors

Clin. Neurophysiol.

(2000)

S.M. MohanKumar et al.

Lipopolysaccharide-induced changes in monoamines in specific areas of the brain: blockade by interleukin-1 receptor antagonist

Brain Res.

(1999)

C. Guilleminault

Sleeepwalking and night tremors

R. Ferber

Sleeepwalking, confusional arousals, and sleep terrors in the child

P. Masand et al.

Sleepwalking

Am. Fam. Physician

(1995)

F. Espa et al.

Arousal reactions in sleepwalking and night terrors in adults: the role of respiratory events

Sleep

(2002)

C. Guilleminault et al.

Sleepwalking and sleep terrors in prepubertal children: what triggers them?

Pediatrics

(2003)

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Citation Excerpt :
The preservation of stage N3 (slow wave) sleep that occurs with zolpidem relative to traditional benzodiazepines might increase the likelihood of NREM parasomnias, as these events most commonly arise from slow wave sleep.15,16 Serotonergic dysfunction may be involved in pathogenesis of sleep walking.17 The findings of an epidemiologic study suggest that SSRI use was particularly associated with SRED.

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Serotonergic hypothesis of sleepwalking

Summary

Section snippets

The characteristic of sleepwalking

Etiology of sleepwalking

The role of serotonergic neurons in chemoreception

The role of serotonin in control of motor activity

The limited role of serotonin in arousal

The role of serotonin in pathophysiology of sleepwalking

Conclusions

Lancet

Brain Res. Rev.

Respir. Physiol.

Neuropsychopharmacology

Brain Res.

Brain Res.

Brain Res.

Neuropsychopharmacology

Prog. Neurobiol.

Eur J Pharmacol

Clin. Neurophysiol.

Brain Res.

Sleeepwalking and night tremors

Sleeepwalking, confusional arousals, and sleep terrors in the child

Sleepwalking

Am. Fam. Physician

Arousal reactions in sleepwalking and night terrors in adults: the role of respiratory events

Sleep

Sleepwalking and sleep terrors in prepubertal children: what triggers them?

Pediatrics