Serotonin in the context of "Rapid eye movement sleep"

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⭐ Core Definition: Serotonin

Serotonin (/ˌsɛrəˈtnɪn, ˌsɪərə-/), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, memory, and physiological processes such as vomiting and vasoconstriction. In the CNS, serotonin regulates mood, appetite, and sleep.

Most of the body's serotonin—about 90%—is synthesized in the gastrointestinal tract by enterochromaffin cells, where it regulates intestinal movements. It is also produced in smaller amounts in the brainstem's raphe nuclei, the skin's Merkel cells, pulmonary neuroendocrine cells, and taste receptor cells of the tongue. Once secreted, serotonin is taken up by platelets in the blood, which release it during clotting to promote vasoconstriction and platelet aggregation. Around 8% of the body's serotonin is stored in platelets, and 1–2% is found in the CNS.

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Serotonin in the context of Pineal gland

The pineal gland (also known as the pineal body or epiphysis cerebri) is a small endocrine gland in the brain of most vertebrates. It produces melatonin, a serotonin-derived hormone, which modulates sleep patterns following the diurnal cycles. The shape of the gland resembles a pine cone, which gives it its name. The pineal gland is located in the epithalamus, near the center of the brain, between the two hemispheres, tucked in a groove where the two halves of the thalamus join. It is one of the neuroendocrine secretory circumventricular organs in which capillaries are mostly permeable to solutes in the blood.

The pineal gland is present in almost all vertebrates, but is absent in protochordates, in which there is a simple pineal homologue. The hagfish, archaic vertebrates, lack a pineal gland. In some species of amphibians and reptiles, the gland is linked to a light-sensing organ, variously called the parietal eye, the pineal eye or the third eye. Reconstruction of the biological evolution pattern suggests that the pineal gland was originally a kind of atrophied photoreceptor that developed into a neuroendocrine organ.

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Serotonin in the context of Fight-or-flight response

The fight-or-flight or the fight-flight-freeze-or-fawn (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first described by Walter Bradford Cannon in 1914 to which he referred to as "the necessities of fighting or flight" in 1915. His theory states that animals react to threats with a general discharge of the sympathetic nervous system, preparing the animal for fighting or fleeing. More specifically, the adrenal medulla produces a hormonal cascade that results in the secretion of catecholamines, especially norepinephrine and epinephrine. The hormones estrogen, testosterone, and cortisol, as well as the neurotransmitters dopamine and serotonin, also affect how organisms react to stress. The hormone osteocalcin might also play a part.

This response is recognised as the first stage of the general adaptation syndrome that regulates stress responses among vertebrates and other organisms.

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Serotonin in the context of Hallucinogen

Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Hallucinogens are often categorized as either being psychedelics, dissociatives, or deliriants, but not all hallucinogens fall into these three classes.

Examples of hallucinogens include psychedelics or serotonin 5-HT2A receptor agonists like LSD, psilocybin, mescaline, and DMT; dissociatives or NMDA receptor antagonists like ketamine, PCP, DXM, and nitrous oxide; deliriants or antimuscarinics like scopolamine and diphenhydramine; cannabinoids or cannabinoid CB1 receptor agonists like THC, nabilone, and JWH-018; κ-opioid receptor agonists like salvinorin A and pentazocine; GABAA receptor agonists like muscimol and gaboxadol; oneirogens like ibogaine and harmaline; and others like nutmeg, carbogen, glaucine, and hallucinogenic bolete mushrooms.

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Serotonin in the context of Mescaline

Mescaline, also known as mescalin or mezcalin, and in chemical terms 3,4,5-trimethoxyphenethylamine, is a naturally occurring psychedelic protoalkaloid of the substituted phenethylamine class, found in cacti like peyote (Lophophora williamsii) and San Pedro (certain species of the genus Echinopsis) and known for its serotonergic hallucinogenic effects.

Mescaline is typically taken orally and used recreationally, spiritually, and medically, with psychedelic effects occurring at doses from 100 to 1,000 mg, including microdosing below 75 mg, and it can be consumed in pure form or via mescaline-containing cacti. Mescaline induces a psychedelic experience characterized by vivid visual patterns, altered perception of time and self, synesthesia, and spiritual effects, with an onset of 0.5 to 0.9 hours and a duration that increases with dose, ranging from about 6 to 14 hours. Ketanserin blocks mescaline’s psychoactive effects, and while it's unclear if mescaline is metabolized by monoamine oxidase enzymes, preliminary evidence suggests harmala alkaloids may potentiate its effects.

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Serotonin in the context of Lysergic acid diethylamide

Lysergic acid diethylamide, commonly known as LSD (from German Lysergsäurediethylamid) and by the slang names acid and lucy, is a semisynthetic hallucinogenic drug derived from ergot, known for its powerful psychological effects and serotonergic activity. It was historically used in psychiatry and 1960s counterculture; it is currently legally restricted but experiencing renewed scientific interest and increasing use.

When taken orally, LSD has an onset of action within 0.4 to 1.0 hours (range: 0.1–1.8 hours) and a duration of effect lasting 7 to 12 hours (range: 4–22 hours). It is commonly administered via tabs of blotter paper. LSD is extremely potent, with noticeable effects at doses as low as 20 micrograms and is sometimes taken in much smaller amounts for microdosing. Despite widespread use, no fatal human overdoses have been documented. LSD is mainly used recreationally or for spiritual purposes. LSD can cause mystical experiences. LSD exerts its effects primarily through high-affinity binding to several serotonin receptors, especially 5-HT2A, and to a lesser extent dopaminergic and adrenergic receptors. LSD reduces oscillatory power in the brain's default mode network and flattens brain hierarchy. At higher doses, it can induce visual and auditory hallucinations, ego dissolution, and anxiety. LSD use can cause adverse psychological effects such as paranoia and delusions and may lead to persistent visual disturbances known as hallucinogen persisting perception disorder (HPPD).

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Serotonin in the context of Psilocybin

Psilocybin, also known as 4-phosphoryloxy-N,N-dimethyltryptamine (4-PO-DMT), is a naturally occurring tryptamine alkaloid and investigational drug found in more than 200 species of mushrooms, with hallucinogenic and serotonergic effects. Effects include euphoria, changes in perception, a distorted sense of time (via brain desynchronization), and perceived spiritual experiences. It can also cause adverse reactions such as nausea and panic attacks.

Psilocybin is a prodrug of psilocin. That is, the compound itself is biologically inactive but quickly converted by the body to psilocin. Psilocybin is transformed into psilocin by dephosphorylation mediated via phosphatase enzymes. Psilocin is chemically related to the neurotransmitter serotonin and acts as a non-selective agonist of the serotonin receptors. Activation of one serotonin receptor, the serotonin 5-HT2A receptor, is specifically responsible for the hallucinogenic effects of psilocin and other serotonergic psychedelics. Psilocybin is usually taken orally. By this route, its onset is about 20 to 50 minutes, peak effects occur after about 1 to 2 hours, and its duration is about 4 to 6 hours.

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Serotonin in the context of Enteric nervous system

The enteric nervous system (ENS) is one of the three divisions of the autonomic nervous system (ANS), the others being the sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS). It consists of a mesh-like system of neurons that governs the function of the gastrointestinal tract. The ENS is nicknamed the "second brain". It is derived from neural crest cells.

The enteric nervous system is capable of operating independently of the brain and spinal cord, but is thought to rely on innervation from the vagus nerve and prevertebral ganglia in healthy subjects. However, studies have shown that the system is operable with a severed vagus nerve. The neurons of the enteric nervous system control the motor functions of the system, in addition to the secretion of gastrointestinal enzymes. These neurons communicate through many neurotransmitters similar to the CNS, including acetylcholine, dopamine, and serotonin. The large presence of serotonin and dopamine in the intestines are key areas of research for neurogastroenterology.

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Serotonin in the context of Neuromodulation

Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfiguring synaptic connectivity.

Major neuromodulators in the central nervous system include: dopamine, serotonin, acetylcholine, histamine, norepinephrine, nitric oxide, and several neuropeptides. Cannabinoids can also be powerful CNS neuromodulators. Neuromodulators can be packaged into vesicles and released by neurons, secreted as hormones and delivered through the circulatory system. A neuromodulator can be conceptualized as a neurotransmitter that is not reabsorbed by the pre-synaptic neuron or broken down into a metabolite. Some neuromodulators end up spending a significant amount of time in the cerebrospinal fluid (CSF), influencing (or "modulating") the activity of several other neurons in the brain.

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Serotonin in the context of Arousal

Arousal is the physiological and psychological state of being awoken or of sense organs stimulated to a point of perception. It involves activation of the ascending reticular activating system (ARAS) in the brain, which mediates wakefulness, the autonomic nervous system, and the endocrine system, leading to increased heart rate and blood pressure and a condition of sensory alertness, desire, mobility, and reactivity.

Arousal is mediated by several neural systems. Wakefulness is regulated by the ARAS, which is composed of projections from five major neurotransmitter systems that originate in the brainstem and form connections extending throughout the cortex; activity within the ARAS is regulated by neurons that release the neurotransmitters norepinephrine, acetylcholine, dopamine, serotonin and histamine.

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