Serotonin-2 Receptors and Human Sleep Effect of a Selective Antagonist on EEG Power Spectra

Landolt, Hans‐Peter; Meier, Viola Sophie; Burgess, Helen J.; Finelli, Luca A.; Cattelin, F; Achermann, Peter; Borbély, Alexander A.

doi:10.1016/s0893-133x(99)00052-4

Cited by 101 publications

(71 citation statements)

References 36 publications

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“…5-HT 1A agonists have been shown to suppress REM sleep (Driver et al 1995;Gillin et al 1994). Regarding SWS, drugs antagonising 5-HT 2A or 5-HT 2C demonstrate an enhancing effect on SWS (Landolt et al 1999;Sharpley et al 1994), whereas 5-HT 2C agonists appear to lower SWS (Katsuda et al 1993).…”

Section: Discussionmentioning

confidence: 99%

“…Both the firing of serotonergic neurons in the raphe nuclei and serotonin release increase during waking, decrease in non-REM sleep and are absent during the REM stage (McGinty and Harper 1976). This regulation mechanism is very complex and involves the interplay of several serotonin receptor subtypes, with 5-HT 1A agonism suppressing REM sleep (Driver et al 1995), 5-HT 2A , 5-HT 2C antagonism enhancing slow-wave sleep (SWS) (Landolt et al 1999) and 5-HT 2C agonism decreasing SWS (Katsuda et al 1993).…”

Section: Introductionmentioning

confidence: 99%

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Daytime Ayahuasca administration modulates REM and slow-wave sleep in healthy volunteers

et al. 2007

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Objectives Ayahuasca is a traditional South American psychoactive beverage and the central sacrament of Brazilianbased religious groups, with followers in Europe and the United States. The tea contains the psychedelic indole N, N-dimethyltryptamine (DMT) and β-carboline alkaloids with monoamine oxidase-inhibiting properties that render DMT orally active. DMT interacts with serotonergic neurotransmission acting as a partial agonist at 5-HT 1A and 5-HT 2A/2C receptor sites. Given the role played by serotonin in the regulation of the sleep/wake cycle, we investigated the effects of daytime ayahuasca consumption in sleep parameters. Measurements and results Subjective sleep quality, polysomnography (PSG), and spectral analysis were assessed in a group of 22 healthy male volunteers after the administration of a placebo, an ayahuasca dose equivalent to 1 mg DMT kg −1 body weight, and 20 mg d-amphetamine, a proaminergic drug, as a positive control. Results show that ayahuasca did not induce any subjectively perceived deterioration of sleep quality or PSG-measured disruptions of sleep initiation or maintenance, in contrast with damphetamine, which delayed sleep initiation, disrupted sleep maintenance, induced a predominance of 'light' vs 'deep' sleep and significantly impaired subjective sleep quality. PSG analysis also showed that similarly to damphetamine, ayahuasca inhibits rapid eye movement (REM) sleep, decreasing its duration, both in absolute values and as a percentage of total sleep time, and shows a trend increase in its onset latency. Spectral analysis showed that d-amphetamine and ayahuasca increased power in the high frequency range, mainly during stage 2. Remarkably, whereas slow-wave sleep (SWS) power in the first night cycle, an indicator of sleep pressure, was decreased by d-amphetamine, ayahuasca enhanced power in this frequency band.Conclusions Results show that daytime serotonergic psychedelic drug administration leads to measurable changes in PSG and sleep power spectrum and suggest an interaction between these drugs and brain circuits modulating REM and SWS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Daytime Ayahuasca administration modulates REM and slow-wave sleep in healthy volunteers

et al. 2007

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“…Moreover, sleep disturbances (Landolt et al, 1999) and sexual dysfunction (Sargent et al, 1998) are preferentially associated with the 5-HT2A receptor and it has been reported that SSRI-induced gastrointestinal side effects are mediated by the 5-HT3 receptor (Bergeron and Blier, 1994). To our knowledge, there have been no previous studies investigating the relationship between polymorphisms of the 5-HT3A and 3B genes and the gastrointestinal side effects induced by SSRI.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the 5-Hydroxytryptamine 2A Receptor and CytochromeP4502D6 Genes Synergistically Predict Fluvoxamine-Induced Side Effects in Japanese Depressed Patients

Suzuki

Sawamura

Someya

2005

Neuropsychopharmacol

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5-Hydroxytryptamine (5-HT) receptors are thought to be associated with the gastrointestinal side effects induced by selective serotonin reuptake inhibitors. CytochromeP450 (CYP) 2D6 may also be associated with the side effects induced by fluvoxamine, since the plasma fluvoxamine concentration depends on a CYP2D6 gene polymorphism. This study investigated whether 5-HT receptor and CYP2D6 gene polymorphisms could predict the occurrence of the side effects. The effects of 5-HT receptor and CYP2D6 gene polymorphisms on the incidence of gastrointestinal side effects induced by fluvoxamine were investigated in 100 depressed outpatients who gave written consent to participate in the study. The patients visited every 2 weeks until the week 12 end point and the fluvoxamine dose was changed in response to their clinical symptoms. All side effects, including the gastrointestinal side effects, were assessed at each visit. Polymerase chain reaction was used to determine A-1438G of the 5-HT2A receptor, C195T and Pro16Ser of the 5-HT3A receptor, Tyr129Ser of the 5-HT3B receptor, and the *5 and *10 alleles of CYP2D6. Both the A-1438G polymorphism of the 5-HT2A receptor gene and the CYP2D6 gene polymorphism had significant effects on the incidence of gastrointestinal side effects. Cox regression was used to analyze the combination effect of the two polymorphisms on the gastrointestinal side effects. Cox regression analysis showed that lower metabolizers (LMs) of CYP2D6 with the G/G genotype of the 5-HT2A A-1438G polymorphism had a 4.242-fold (P ¼ 0.009) and LMs with the A/G genotype had a 4.147-fold (P ¼ 0.004) higher risk of developing gastrointestinal side effects than normal metabolizers with the A/A genotype. The 5-HT3A and 3B gene polymorphisms had no significant effects on the incidence of gastrointestinal side effects. 5-HT2A receptor and CYP2D6 gene polymorphisms had a synergistic effect for the prediction of fluvoxamine-induced gastrointestinal side effects.

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“…It is unknown whether this polymorphism also modulates availability of other 5-HT receptor subtypes. Notwithstanding, it may contribute to inter-individual differences in the efficacy of currently emerging hypnotics that improve sleep via a serotonergic mechanism of action [140,141].…”

Section: Serotonin Transporter Gene (Slc6a4)mentioning

confidence: 99%

Genotype-Dependent Differences in Sleep, Vigilance, and Response to Stimulants

Landolt

2008

CPD

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Abstract:To better understand the neurobiology of sleep disorders, detailed understanding of circadian and homeostatic sleep-wake regulation in healthy volunteers is mandatory. Sleep physiology and the repercussions of experimentallyinduced sleep deprivation on sleep and waking electroencephalogram (EEG), vigilance and subjective state are highly variable, even in healthy individuals. Accumulating evidence suggests that many aspects of normal sleep-wake regulation are at least in part genetically controlled. Current heritability estimates of sleep phenotypes vary between approximately 20-40 % for habitual sleep duration, to over 90 % for the spectral characteristics of the EEG in nonREM sleep. The molecular mechanisms underlying the trait-like, inter-individual variation are virtually unknown, and the human genetics of normal sleep is only at the beginning of being explored. The first studies identified distinct polymorphisms in genes contributing to the endogenous circadian clock and neurochemical systems previously implicated in sleep-wake regulation, to modulate sleep architecture and sleep EEG, vulnerability to sleep loss, and subjective and objective effects of caffeine on sleep. These insights are reviewed here. They disclose molecular mechanisms contributing to normal sleep-wake regulation in humans, and have potentially important implications for the neurobiology of sleep-wake disorders and their pharmacological treatment.

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Serotonin-2 Receptors and Human Sleep Effect of a Selective Antagonist on EEG Power Spectra

Cited by 101 publications

References 36 publications

Daytime Ayahuasca administration modulates REM and slow-wave sleep in healthy volunteers

Daytime Ayahuasca administration modulates REM and slow-wave sleep in healthy volunteers

Polymorphisms in the 5-Hydroxytryptamine 2A Receptor and CytochromeP4502D6 Genes Synergistically Predict Fluvoxamine-Induced Side Effects in Japanese Depressed Patients

Genotype-Dependent Differences in Sleep, Vigilance, and Response to Stimulants

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