ArticlePDF Available


Content may be subject to copyright.
Oncotarget78222 Oncotarget, Vol. 7, No. 48
Serotonin and sleep-promoting neurons
Armelle Rancillac
Serotonin (5-HT) is a monoamine neurotransmitter
that plays major roles in several physiological functions
including circadian rhythmicity, thermoregulation,
emotion, cognition and nociception. The relationship
between 5-HT and sleep was demonstrated by several
experiments. In a particularly elegant one, cats were
rendered insomniac following the injection of a 5-HT
synthesis inhibitor. In this model, the preoptic area of
the hypothalamus containing the ventrolateral preoptic
area (VLPO) was the only brain region in which
microinjections of the 5-HT precursor could restore long
periods of sleep [1]. The VLPO being the main brain
structure inducing slow-wave sleep (SWS), it was then
hypothesized that 5-HT modulation of neuronal activity
in this structure is essential for sleep regulation. However,
the mechanisms involved in the physiological role of 5-HT
within the VLPO remained largely unknown.
The VLPO is a small cluster of neurons composed
of different neuronal populations. Five distinct neuronal
classes were recently electrophysiologically dened
[2]. These neuronal populations were morphologically
characterized and were shown to differently respond to
neurotransmitters such as noradrenaline (NA) and 5-HT.
Indeed, sleep-promoting neurons within the VLPO are
usually identied by their inhibitory response to NA,
suggesting that they are maintained silent during waking.
They are either inhibited (Type-1) or excited (Type-2) by
5-HT application [3].
In our paper, the mode of action and the effects
of 5-HT were determined in Type-1 and Type-2 sleep-
promoting neurons. In acute VLPO slices of mouse,
spontaneous and miniatures excitatory and inhibitory
postsynaptic currents were recorded in response to
bath application of 5-HT. We found that 5-HT reduces
frequencies of all these events to Type-1 neurons, whereas
5-HT selectively increases the frequencies of inhibitory
events to Type-2 VLPO neurons [4].
Furthermore, our data shows that Type-1 and
Type-2 sleep-promoting neurons present similar
morphological somatic hallmarks as measured on infrared
microphotography taken prior electrophysiological
recordings. However, we established that the area of
Type-1 neurons was signicantly smaller compared to
Type-2 neurons. Membrane properties of sleep-promoting
neurons were also investigated eletrophysiologically. We
found that the action potential threshold was signicantly
lower in Type-1 compared to Type-2 neurons. As Type-
2 neurons have been previously shown to selectively
respond to an A2A adenosine receptor agonist [3, 5], they
could likely integrate the homeostatic drive associated
with adenosine accumulation during wakefulness, and
rst respond to the serotonergic excitatory inputs. Then,
the activation of Type-2 neurons would decrease the
frequency of GABAergic inputs to Type-1 neurons and
favor their activation. Type-1 VLPO neurons would then
inhibit arousal systems and allow the maintenance of
slow-wave sleep.
Finally, we investigated the molecular diversity of
sleep-promoting neurons using the single-cell RT-PCR
technique to simultaneously detect the expression of the
Figure 1: Schematic drawing depicting the potential
mechanism of the regulation of afferent inputs to
sleep-promoting neurons by 5-HT.
13 serotonergic receptors. We established that 5-HT1
receptors mRNA were only detected in Type-1 neurons,
whereas mRNAs encoding 5-HT2A-C, 5-HT4 and 5-HT7
were equally distributed between Type-1 and Type-
2 VLPO neurons. To conrm the putative expression
of 5-HT1A and 5-HT2C receptors that were the most
frequently amplied mRNA, we applied potent agonist
of these receptors on sleep-promoting neurons. In loose-
patch recordings, we established that the selective 5-HT1A
receptor agonist, the 8-OH-DPAT, decreases the ring
frequency of Type-1 neurons, whereas a 5-HT2C receptor
agonist, PF03246799, enhances the ring frequency of
Type-2 neurons. Interestingly, we also observed that the
decreased ring rate induced by 5-HT application in Type-
1 neurons was subsequently followed by a small increased
of their ring rate and that PF03246799 application
could also increase the ring rate in a subset of Type-1
neurons. Physiologically, we hypothesize that afferent
serotonergic inputs to the VLPO could exert a complex
and ne control of sleep-promoting neurons. Nevertheless,
it appears from the literature that systemic injections of
a 5-HT agonist could produce opposite effects on sleep
amounts, depending on the concentration used and on the
time of the sleep-wake cycle during which the treatment
was administered [6, 7]. These studies suggest a circadian
modulation of serotonergic receptor function.
Altogether, our results established
electrophysiological, morphological and molecular
differences between these two neuronal types of sleep-
promoting neurons. Type-2 neurons being more excitable,
they could likely integrate the homeostatic drive of sleep
and be involved in the preparation and initiation of sleep
(permissive neurons). Then, their activation could decrease
the frequency of inhibitory inputs to Type-1 neurons to
favor their activation. Type-1 VLPO neurons would then
inhibit arousal systems and allow the maintenance of SWS
(executive neurons, Figure 1).
Our work provides new insights regarding sleep
regulation by 5-HT and propose distinct roles for Type-
1 and Type-2 neurons. Furthermore, we established that
sleep-promoting neurons frequently express 5-HT2C
receptors that could represent a molecular target for the
development of safer and more effective sleep-promoting
medication to treat insomnia and to improve quality of
Armelle Rancillac: Neuroglial Interactions in Cerebral
Physiopathology, CIRB, Rouach’s team, CNRS UMR /
Inserm, Collège de France, place Marcelin Berthelot, Paris
Correspondence to: Armelle Rancillac, email armelle.rancil-
Keywords: VLPO, slow-wave sleep (SWS), non-rapid eye
movement sleep (NREM), 5-HT2C receptor, 5-HT1A receptor
Received: November 08, 2016
Published: November 16, 2016
1. Denoyer M, et al. Neuroscience. 1989; 28:83-94.
2. Dubourget R, et al. Brain Structure and Function. 2016;
3. Gallopin T, et al. Neuroscience. 2005; 134:1377-1390.
4. Sangare A, et al. Neuropharmacology. 2016; 109:29-40.
5. Scharbarg E, et al. Scientic Report. 2016; 6:19107.
6. Monti JM, Sleep Medicine Reviews. 2011; 15:269-281.
7. Morrow JD, et al. Sleep. 2008; 31:21-33.
... Activation of the dorsal raphe nucleus promotes wakefulness [73]. The ventrolateral preoptic area (VLPO) is the main brain area that promotes SWS [74]. It has been reported that serotonergic modulation of neuronal activity in the VLPO is essential for sleep regulation [75]. ...
... The VLPO is a small cluster of neurons that is consisted of various neuronal populations. Electrophysiological reports have shown five distinct neuronal populations in the VLPO [74]. Furthermore, it has been shown that these neuronal populations are morphologically different and induce different responses to neurotransmitters such as noradrenaline and serotonin. ...
... Furthermore, it has been shown that these neuronal populations are morphologically different and induce different responses to neurotransmitters such as noradrenaline and serotonin. In fact, sleep-promoting neurons in the VLPO are usually identified by their inhibitory responses to noradrenaline [74]. These neuronal population are inhibited (Type-1) or excited (Type-2) by serotonin [76]. ...
Serotonin is an important neurotransmitter with various receptors and wide-range effects on physiological processes and cognitive functions including sleep, learning, and memory. In this review study, we aimed to discuss the role of serotonergic receptors in modulating sleep–wake cycle, and learning and memory function. Furthermore, we mentioned to sleep deprivation, its effects on memory function, and the potential interaction with serotonin. Although there are thousands of research articles focusing on the relationship between sleep and serotonin; however, the pattern of serotonergic function in sleep deprivation is inconsistent and it seems that serotonin has not a certain role in the effects of sleep deprivation on memory function. Also, we found that the injection type of serotonergic agents (systemic or local), the doses of these drugs (dose-dependent effects), and up- or down-regulation of serotonergic receptors during training with various memory tasks are important issues that can be involved in the effects of serotonergic signaling on sleep–wake cycle, memory function, and sleep deprivation-induced memory impairments. This comprehensive review was conducted in the PubMed, Scopus, and ScienceDirect databases in June and July 2021, by searching keywords sleep, sleep deprivation, memory, and serotonin.
... It is currently accepted that serotonin promotes wakefulness, inhibits REM sleep, and induces slow wave sleep (Monti, 2011;Rancillac, 2016). Serotonin is predominantly synthesized in the raphe nuclei of the brainstem and is projected extensively into multiple cortical and subcortical structures in a sprinkler-type fashion to arouse wakefulness (Daubert and Condron, 2010). ...
... In fact, considering the complex innervation of serotonergic neurons, based on the available evidence, it is difficult to distinctly illustrate the role of serotonin decline in age-related sleep disturbances. Still, existing evidence, such as serotonin activating sleep-promoting neurons in VLPO in mice (Rancillac, 2016), local blockage of serotonergic transmission in the forebrain/preoptic areas disrupting the circadian clocks of mice (Miyamoto et al., 2012), and serotonin-enhancing circadian responses to light in hamsters (Smith et al., 2015) partially explain the underlying mechanisms. ...
With aging, various factors deteriorate the normal sleep process that is essential for the restoration of functional and physical performance. Due to aging-related diseases, life changes, or aging itself, disturbances in normal sleep cycles can profoundly affect healthy aging. To understand the interconnections between aging and the factors influencing sleep, with emerging evidence accumulated in recent years, this study elaborates on the roles of aging in sleep from four perspectives: cortical thinning, white matter degeneration, neurotransmitter dysregulation, and circadian disorganization. In brief, with aging, cortical thinning can be induced by the deposition of neurotoxic substances, and white matter degeneration can be induced by vascular abnormalities. These alterations emerging in the brain jointly disrupt sleep spindles and slow waves, leading to sleep disturbances. Age-related dysregulation in neurotransmitters (including galanin, orexin, serotonin, and adenosine) directly impairs the sleep modulation system. Disorganization in the circadian system consisting of suprachiasmatic nucleus dysfunction, reduced light transmission, and local circadian clock disruption collectively interrupts circadian rhythms, also causing sleep disturbances in the older. Of note is the bidirectional relationship between aging and sleep, which required us to examine this issue from different perspectives.
... As reported in Table 1 and Figure 1, we would expect drugs that increase concentrations of the catecholamines (noradrenaline and dopamine) or histamine to induce or enhance wakefulness, and those that increase GABA concentration to induce or enhance sleep. Serotonergic stimulation yields complex and seemingly opposing effects on the sleep-wake cycle (244), possibly due to circadian modulation of serotonergic receptor function (253), and hence, drugs that increase concentrations of serotonin, or both catecholamines and serotonin, like some antidepressants, might have mixed effects. As summarized in Table 2, the gabapentinoids, which reduce excitatory catecholamines, enhance sleep. ...
We review the known physiological mechanisms underpinning all of pain processing, sleep regulation, and pharmacology of analgesics prescribed for chronic pain. In particular, we describe how commonly prescribed analgesics act in sleep-wake neural pathways, with potential unintended impact on sleep and/or wake function. Sleep disruption, whether pain- or drug-induced, negatively impacts quality of life, mental and physical health. In the context of chronic pain, poor sleep quality heightens pain sensitivity and may affect analgesic function, potentially resulting in further analgesic need. Clinicians already have to consider factors including efficacy, abuse potential, and likely side effects when making analgesic prescribing choices. We propose that analgesic-related sleep disruption should also be considered. The neurochemical mechanisms underlying the reciprocal relationship between pain and sleep are poorly understood, and studies investigating sleep in those with specific chronic pain conditions (including those with comorbidities) are lacking. We emphasize the importance of further work to clarify the effects (intended and unintended) of each analgesic class to inform personalized treatment decisions in patients with chronic pain. © 2021 American Physiological Society. Compr Physiol 11:1-31, 2021.
... Once thought to be the primary neurotransmitter of sleep (88), the role of serotonin in the sleep-wake cycle is now understood as more complex, being involved in various processes necessary for both sleep and wake. Serotonin has been hypothesized to regulate neuronal activity in the ventrolateral preoptic area of the brain, the main structure responsible for inducing slow-wave sleep (SWS) (91). High levels of neuronal activity in this region during sleep suggest a role of serotonin in the induction of the sleep cycle. ...
Two factors intrinsic to health are diet and sleep. These two behaviors may well influence one another. Indeed, that insufficient sleep adversely impacts dietary intakes is well documented. On the other hand, diet may influence sleep via melatonin and its biosynthesis from tryptophan. Experimental data exist indicating that provision of specific foods rich in tryptophan or melatonin can improve sleep quality. Whole diets rich in fruits, vegetables, legumes, and other sources of dietary tryptophan and melatonin have been shown to predict favorable sleep outcomes. Although clinical trials are needed to confirm a causal impact of dietary patterns on sleep and elucidate underlying mechanisms, available data illustrate a cyclical relation between these lifestyle factors. We recommend adopting a healthful diet to improve sleep, which may further promote sustained favorable dietary practices. Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see for revised estimates.
... For instance, several neuroanatomical nuclei, such as basal forebrain, hypothalamus, pons, among others, exert influence in sleep modulation [13][14][15][16][17][18]. In addition, the sleep-wake cycle is under control of several endogenous molecules such as neurotransmitters, peptides, lipids, hormones, as well as the expression of sleep-related genes [19][20][21][22][23][24]. In mammals studied so far, sleep is associated with behavioural quiescence, closed eyes, and speciespecific postural recumbence [25]. ...
Objective: Aging is a natural biological phenomenon that occurs in human beings. With increasing of age, there is an appearance of deleterious changes related with progression onto pathological conditions, including hypertension, heart disease, diabetes, hearing and vision impairments, as well as sleep disorders. It is important to recognize that some sleep disturbances reported by aged subjects include insomnia, obstructive sleep apnea, restless legs syndrome, among others. Moreover, accumulating evidence indicates that coexistence of medical issues with sleep disorders constitutes clinical challenges for treatment of comorbidities in elderly. Here, we have attempted to review and summarize the available literature that assess the sleep disturbances in aging. In addition, we highlight the management of sleep disorders associated with aging. Due to particular health condition of aged adults, the development of effective pharmacological interventions for sleep disorders treatment in aging is warranted. Method: Review of studies retrieved from the PubMed. Results: The sleep-wake cycle includes abnormalities classified as sleep disorders. Comorbidity between sleep disturbances and aging-related health issues will represent a public health challenge to be address in the near future. Moreover, this scenario will suggest an area that require further drug investigation and design of new pharmacological and pharmaceutical strategies to treat sleep disorders in elderly population. Conclusion: The review highlights the sleep disturbances in aging. We focus on current knowledgment in medicinal chemistry and further design of new treatments tools for managing sleep disturbances in aged population.
The mental health of the older adult population requires the practitioner to invest time in understanding the life events and lifestyle of their patients in order to adequately assess and support this key area of health. Older adults often find themselves in highly stressful environments. Big life stresses such as the loss of a spouse or loved ones, financial strain, health concerns, polypharmacy, and social isolation are common and can trigger imbalances in mental health. Even in patients with previously well-managed psychological conditions, medications begin to fail, new triggers create a higher need, and additional compromise in health ignites a mental health crisis. Complementing psychotherapy with nutritional improvements, well-placed nutraceuticals, and safe movement such as Tai Chi or swimming addresses the root causes of symptoms. Paying attention to the interconnection between brain health and gut health is critical to addressing the root causes driving the inflammation, toxicity, and hormonal imbalances that lay the foundation for psychological distress. Recognizing the bidirectional information highway between the gut and the brain, the enteric nervous system with the longest nerve in the body called the vagus nerve, is the key to understanding the interconnectedness of the two and, thus, supporting healing in the seat of our psychological state, the brain. The manifestations of various imbalances in the gut, inflammatory responses, and detoxification pathways can manifest as psychological distress. The most common psychological disorders in the aging adult population are depression, anxiety, and insomnia.
Full-text available
Background: The beneficial impact of adherence to a DASH diet on several metabolic conditions and psychological well-being has been shown previously. Dietary modification can affect sleep quality. Thus, the aim of this present study was to investigate the correlation between adherence to the DASH diet and daytime sleepiness score in adolescent girls. Methods: A total of 535 adolescent girls aged between 12 and 18 years old were recruited from different regions of Khorasan Razavi in northeastern of Iran, using a random cluster sampling method. DASH scores were determined according to the method of Fung et al. A Persian translation of the Epworth Sleepiness Scale (ESS-IR) was used to assess of daytime sleepiness. To investigate the correlation between DASH-style diet and daytime sleepiness score, we applied logistic regression analysis in crude and adjusted models. Results: As may be expected, participants with the greatest adherence to the DASH diet had significantly higher intakes of fruits, vegetables, low-fat dairy products, fish and nuts, and lower consumption of refined grains, red and processed meat, sugar-sweetened beverages and sweets. There was an inverse correlation between adherence to the DASH-style diet and scores for daytime sleepiness in crude model (β= -0.12; P=0.005). These findings were remained significant after adjustment for confounding variables (β= -0.08 P=0.04). Conclusion: There is an inverse correlation between adherence to DASH diet and daytime sleepiness score. Further studies, particularly longitudinal studies, are required to determine whether dietary intervention may improve daytime sleepiness.
Sleep is an active state that is as complex as wakefulness. The main tasks of sleep are the adaptation and restoration of physical and mental strength. Sleep regulation is a complex multimodal process involving not only neurotransmitters, but also releasing­factors, hormones, cytokines, signaling molecules and metabolites. Having a lot of physiological effects, postoperative sleep plays a role not only in quality of life, but also in the recovery of the patient. The characteristics of the patient, the type of surgical intervention, the methods of anesthesia and their interaction affects postoperative sleep, but the relationship and the level of influence of these factors are not clear. Therefore, given the high prevalence of postoperative insomnia, this problem is relevant for modern anesthesiology.
3,4-Methylenedioxymethamphetamine (MDMA) affects monoaminergic pathways that play a critical role in sleep-wake cycles. Dopaminergic mechanisms are thought to mediate the sleep-disrupting effects of stimulant drugs. However, the mechanisms underlying the effects of MDMA on sleep-wake cycles and the effects of R (-) MDMA, a stereoisomer that lacks dopaminergic activity, on sleep remain unknown. The aim of the present study was to investigate the effects of racemic MDMA and R (-) MDMA on daytime activity and sleep-like parameters evaluated with actigraphy in adult rhesus macaques ( Macaca mulatta , n = 6). Actiwatch monitors were attached to the monkeys’ collars and actigraphy recording was conducted during baseline conditions and after the administration of acute intramuscular injections of saline (vehicle), racemic MDMA (0.3, 1.0, or 1.7 mg/kg), or R (-) MDMA (0.3, 1.0, or 1.7 mg/kg) at 9 or 16 h (3 h before “lights off”). Morning treatments had no effects on sleep-like parameters. Racemic MDMA decreased general daytime activity during the first hour after injection and increased daytime activity at 3 hr posttreatment. Although afternoon administration of racemic MDMA increased sleep latency, it improved other sleep parameters, decreasing wake time after sleep onset (WASO) and increasing sleep efficiency for subjects with low baseline sleep efficiency. Afternoon treatment with R(-) MDMA improved sleep measures, increasing sleep efficiency and decreasing sleep latency and WASO, while having no effects on daytime activity. The stimulant and sleep-disrupting effects of racemic MDMA are likely mediated by dopaminergic and noradrenergic mechanisms, while serotonergic pathways appear to be involved in the sleep-promoting effects of MDMA.
Full-text available
Sleep has been hypothesised to maintain a close relationship with metabolism. Here we focus on the brain structure that triggers slow-wave sleep, the ventrolateral preoptic nucleus (VLPO), to explore the cellular and molecular signalling pathways recruited by an increase in glucose concentration. We used infrared videomicroscopy on ex vivo brain slices to establish that glucose induces vasodilations specifically in the VLPO via the astrocytic release of adenosine. Real-time detection by in situ purine biosensors further revealed that the adenosine level doubles in response to glucose, and triples during the wakefulness period. Finally, patch-clamp recordings uncovered the depolarizing effect of adenosine and its A2A receptor agonist, CGS-21680, on sleep-promoting VLPO neurons. Altogether, our results provide new insights into the metabolically driven release of adenosine. We hypothesise that adenosine adjusts the local energy supply to local neuronal activity in response to glucose. This pathway could contribute to sleep-wake transition and sleep intensity.
Full-text available
Recent research has shown that neurons in the ventrolateral preoptic nucleus are crucial for sleep by inhibiting wake-promoting systems, but the process that triggers their activation at sleep onset remains to be established. Since evidence indicates that sleep induced by adenosine, an endogenous sleep-promoting substance, requires activation of brain A(2A) receptors, we examined the hypothesis that adenosine could activate ventrolateral preoptic nucleus sleep neurons via A(2A) adenosine receptors in rat brain slices. Following on from our initial in vitro identification of these neurons as uniformly inhibited by noradrenaline and acetylcholine arousal transmitters, we established that the ventrolateral preoptic nucleus comprises two intermingled subtypes of sleep neurons, differing in their firing responses to serotonin, inducing either an inhibition (Type-1 cells) or an excitation (Type-2 cells). Since both cell types contained galanin and expressed glutamic acid decarboxylase-65/67 mRNAs, they potentially correspond to the sleep promoting neurons inhibiting arousal systems. Our pharmacological investigations using A(1) and A(2A) adenosine receptors agonists and antagonists further revealed that only Type-2 neurons were excited by adenosine via a postsynaptic activation of A(2A) adenosine receptors. Hence, the present study is the first demonstration of a direct activation of the sleep neurons by adenosine. Our results further support the cellular and functional heterogeneity of the sleep neurons, which could enable their differential contribution to the regulation of sleep. Adenosine and serotonin progressively accumulate during arousal. We propose that Type-2 neurons, which respond to these homeostatic signals by increasing their firing are involved in sleep induction. In contrast, Type-1 neurons would likely play a role in the consolidation of sleep.
Full-text available
Extensive data implicate serotonin (5-hydroxytryptamine [5-HT]) in the regulation of sleep. Jouvet has hypothesized that 5-HT promotes wakefulness, yet is necessary for subsequent non-rapid eye movement (NREM) sleep, actions he proposes to be mediated by sleep factors. Studies in rat support this dual role for 5-HT. The objectives of this study were to (1) determine effects of serotonergic activation on sleep of mice and (2) elucidate a potential role for the cytokine interleukin-6 as a sleep factor mediating serotonergic effects on sleep. C57BL/6J and B6.129S6-II6(tm1Kopf)(interleukin-6 knockout [IL-6 KO]) mice were purchased from the Jackson Laboratory and instrumented for recording the electroencephalogram and body temperature. After recovery, separate groups of mice were injected intraperitoneally at either light or dark onset with vehicle or with the 5-HT precursor 5-hydroxytryptophan (5-HTP). Sleep-wake behavior was determined and body temperature recorded for 24 hours after injections. 5-HTP induced hypothermia in both mouse strains. When injected at dark onset, the highest dose of 5-HTP (200 mg/kg) increased NREM sleep. Light onset administration initially increased wakefulness, with increases in NREM sleep apparent only during the subsequent dark period. For most parameters, there were no differences in responses between strains. However IL-6 KO mice at some doses exhibited a greater increase in NREM sleep. 5-HTP alters sleep-wake behavior and body temperature of mice in a manner similar to that of rats. Increases in NREM sleep after 5-HTP are apparent only during the dark period, which may represent a fundamental property of the serotonergic system. These results suggest that 5-HT should not be considered either wake promoting or NREM sleep promoting. Rather, the role of 5-HT in the regulation of sleep-wake behavior must be considered within the context of the degree to which the system is activated and the time at which the activation occurs.
Para-chlorophenylalanine, a blocker of serotonin biosynthesis by inhibiting tryptophan hydroxylase, induced total insomnia which was accompanied in cat by a permanent discharge of ponto-geniculo-occipital activity. L-5-Hydroxytryptophan microinjection (1-4 micrograms/0.5 microliters) in the anterior hypothalamus 72 h after para-chlorophenylalanine administration, restored both slow wave sleep and paradoxical sleep with variable latencies for each state of sleep. On the contrary, ponto-geniculo-occipital activity was never suppressed. The hypnogenic effects of L-5-hydroxytryptophan were always followed by a return of the para-chlorophenylalanine-induced insomnia. On the other hand, the temperature recording did not show any alteration of the cerebral temperature after para-chlorophenylalanine treatment but the subsequent L-5-hydroxytryptophan microinjection was followed by hyperthermia. Using immunohistochemistry for serotonin after intrahypothalamic L-5-hydroxytryptophan microinjection in parachlorophenylalanine-pretreated cat, we defined a restricted region of the anterior hypothalamus possibly responsible for the hypnogenic effect. This region included the lateral hypothalamus and the anterior hypothalamic area. It is suggested that the reversible hypersomnia after L-5-hydroxytryptophan microinjection in the anterior hypothalamus in para-chlorophenylalanine-pretreated cat is due to a neurohormonal action of serotonin: serotonin could act upon the anterior hypothalamus which secondarily inhibits a waking system located in the ventrolateral hypothalamus leading to the appearance of paradoxical sleep.
  • A Sangare
Sangare A, et al. Neuropharmacology. 2016; 109:29-40.
  • E Scharbarg
Scharbarg E, et al. Scientific Report. 2016; 6:19107.
  • J M Monti
Monti JM, Sleep Medicine Reviews. 2011; 15:269-281.
  • R Dubourget
Dubourget R, et al. Brain Structure and Function. 2016; 1-15.