Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a

monoamine neurotransmitter Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines ...

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 The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

enterochromaffin cell Enterochromaffin (EC) cells (also known as Kulchitsky cells) are a type of enteroendocrine cell, and neuroendocrine cell. They reside alongside the epithelium lining the lumen of the digestive tract and play a crucial role in gastrointestinal r ...

s, where it regulates intestinal movements. It is also produced in smaller amounts in the brainstem's

raphe nuclei The raphe nuclei (, "seam") are a moderate-size cluster of nuclei found in the brain stem. They have 5-HT1 receptors which are coupled with Gi/Go-protein-inhibiting adenyl cyclase. They function as autoreceptors in the brain and decrease the ...

, the skin's Merkel cells,

pulmonary neuroendocrine cell Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules (hormones) into the blood. In this way they bri ...

s, and taste receptor cells of the tongue. Once secreted, serotonin is taken up by

platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...

s 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. Serotonin acts as both a vasoconstrictor and vasodilator depending on concentration and context, influencing

hemostasis In biology, hemostasis or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. Hemostasis involves three ...

and blood pressure regulation. It plays a role in stimulating myenteric neurons and enhancing gastrointestinal motility through uptake and release cycles in platelets and surrounding tissue. Biochemically, serotonin is an

indoleamine Indolamines are a family of neurotransmitters that share a common molecular structure. Indolamines are a classification of monoamine neurotransmitter, along with catecholamines and ethylamine derivatives. A common example of an indolamine is the ...

synthesized from

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...

and metabolized primarily in the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

to 5-hydroxyindoleacetic acid (5-HIAA). Serotonin is targeted by several classes of

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

s, including

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...

s (SSRIs) and

serotonin–norepinephrine reuptake inhibitor Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, social phobia, chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopaus ...

s (SNRIs), which block reabsorption in the synapse to elevate its levels. It is found in nearly all bilateral animals, including insects, spiders and worms, and also occurs in

fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...

and

plant Plants are the eukaryotes that form the Kingdom (biology), kingdom Plantae; they are predominantly Photosynthesis, photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with c ...

s. In plants and insect venom, it serves a defensive function by inducing pain. Serotonin released by pathogenic amoebae may cause

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

in the human gut, while its presence in seeds and fruits is thought to stimulate digestion and facilitate seed dispersal.

Molecular structure

Biochemically, the

molecule derives from the amino acid

, via the (rate-limiting)

hydroxylation In chemistry, hydroxylation refers to the installation of a hydroxyl group () into an organic compound. Hydroxylations generate alcohols and phenols, which are very common functional groups. Hydroxylation confers some degree of water-solubility ...

of the 5 position on the ring (forming the intermediate 5-hydroxytryptophan), and then

decarboxylation Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is ...

to produce serotonin. Preferable conformations are defined via ethylamine chain, resulting in six different conformations.

Crystal structure

Serotonin crystallizes in P2₁2₁2₁ chiral space group forming different hydrogen-bonding interactions between serotonin molecules via N-H...O and O-H...N intermolecular bonds. Serotonin also forms several salts, including pharmaceutical formulation of serotonin adipate.

Biological role

Serotonin is involved in numerous physiological processes, including

sleep Sleep is a state of reduced mental and physical activity in which consciousness is altered and certain Sensory nervous system, sensory activity is inhibited. During sleep, there is a marked decrease in muscle activity and interactions with th ...

thermoregulation Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature ...

learning Learning is the process of acquiring new understanding, knowledge, behaviors, skills, value (personal and cultural), values, Attitude (psychology), attitudes, and preferences. The ability to learn is possessed by humans, non-human animals, and ...

and

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembe ...

pain Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...

, (social) behavior,

sexual activity Human sexual activity, human sexual practice or human sexual behaviour is the manner in which humans experience and express their sexuality. People engage in a variety of sexual acts, ranging from activities done alone (e.g., masturbation) t ...

, feeding, motor activity, neural development, and biological rhythms. In less complex animals, such as some

invertebrates Invertebrates are animals that neither develop nor retain a vertebral column (commonly known as a ''spine'' or ''backbone''), which evolved from the notochord. It is a paraphyletic grouping including all animals excluding the chordate subphylum ...

, serotonin regulates feeding and other processes. In plants serotonin synthesis seems to be associated with stress signals. Despite its longstanding prominence in pharmaceutical advertising, the claim that low serotonin levels cause depression is not supported by scientific evidence.

Cellular effects

Serotonin primarily acts through its receptors and its effects depend on which cells and tissues express these receptors. Metabolism involves first

oxidation Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...

monoamine oxidase Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The fi ...

to 5-hydroxyindoleacetaldehyde (5-HIAL). The rate-limiting step is hydride transfer from serotonin to the flavin cofactor. There follows oxidation by

aldehyde dehydrogenase Aldehyde dehydrogenases () are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes (R–C(=O)) to carboxylic acids (R–C(=O)). The oxygen comes from a water molecule. To date, nineteen ALDH genes have ...

(ALDH) to 5-hydroxyindoleacetic acid (), the

indole Indole is an organic compound with the formula . Indole is classified as an aromatic heterocycle. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indoles are derivatives of indole ...

acetic-acid derivative. The latter is then excreted by the kidneys.

Receptors

The

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the central and peripheral nervous systems. They mediate both ex ...

s are located on the

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

nerve cells A neuron (American English), neurone (British English), or nerve cell, is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. They are located in the nervous system and help to ...

and other cell types in animals, and mediate the effects of serotonin as the

endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

and of a broad range of pharmaceutical and

psychedelic drug Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluc ...

s. There are currently 14known serotonin receptors, including the serotonin 5-HT₁ (_1A, _1B, _1D, _1E, _1F), 5-HT₂ (_2A, _2B, _2C), 5-HT₃, 5-HT₄, 5-HT₅ (_5A, _5B), 5-HT₆, and 5-HT₇ receptors. Except for the serotonin 5-HT₃ receptor, a ligand-gated

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

, all other 5-HT receptors are G-protein-coupled receptors (also called seven-transmembrane, or heptahelical receptors) that activate an

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

second messenger Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form of cell signaling, encompassing both first m ...

cascade. The 5-HT_5B receptor is present in rodents but not in humans. In addition to the serotonin receptors, serotonin is an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the

trace amine-associated receptor 1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is a primarily intracellular amine-activated and G protein-coupled receptor (GPCR) that is p ...

(TAAR1) in some species. It is a weak TAAR1

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

in rats, but is inactive at the TAAR1 in mice and humans. The

cryo-EM Cryogenic electron microscopy (cryo-EM) is a transmission electron microscopy technique applied to samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An ...

structure A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

s of the serotonin 5-HT_2A receptor with serotonin, as well as with various

serotonergic psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

s, have been solved and published by Bryan L. Roth and colleagues.

Termination

Serotonergic action is terminated primarily via uptake of 5-HT from the synapse. This is accomplished through the specific

monoamine transporter Monoamine transporters (MATs) are proteins that function as integral Cell membrane, plasma-membrane Neurotransmitter transporter, transporters to regulate concentrations of extracellular monoamine neurotransmitters. The three major classes are se ...

for 5-HT, SERT, on the presynaptic neuron. Various agents can inhibit 5-HT reuptake, including

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

dextromethorphan Dextromethorphan, sold under the brand name Robitussin among others, is a cough suppressant used in many cough and Common cold, cold medicines. In 2022, the US Food and Drug Administration (FDA) approved the combination dextromethorphan/bupropi ...

(an antitussive),

tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains ...

and

s (SSRIs). A 2006 study found that a significant portion of 5-HT's synaptic clearance is due to the selective activity of the plasma membrane monoamine transporter (PMAT) which actively transports the molecule across the membrane and back into the presynaptic cell. In contrast to the high affinity of SERT, the PMAT has been identified as a low-affinity transporter, with an apparent ''K''_m of 114 micromoles/l for serotonin, which is approximately 230 times higher than that of SERT. However, the PMAT, despite its relatively low serotonergic affinity, has a considerably higher transport "capacity" than SERT, "resulting in roughly comparable uptake efficiencies to SERT ... in heterologous expression systems." The study also suggests that the administration of SSRIs such as

fluoxetine Fluoxetine, sold under the brand name Prozac, among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used for the treatment of major depressive disorder, Anxiety disorder, anx ...

and

sertraline Sertraline, sold under the brand name Zoloft among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used to treat major depressive disorder, generalized anxiety disorder, socia ...

may be associated with an inhibitory effect on PMAT activity when used at higher than normal dosages ( IC₅₀ test values used in trials were 3–4 fold higher than typical prescriptive dosage).

Serotonylation

Serotonin can also signal through a nonreceptor mechanism called serotonylation, in which serotonin modifies proteins. This process underlies serotonin's effects upon platelet-forming cells (

thrombocyte Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cytop ...

s) in which it links to the modification of signaling enzymes called

GTPase GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a ...

s that then trigger the release of vesicle contents by

exocytosis Exocytosis is a term for the active transport process that transports large molecules from cell to the extracellular area. Hormones, proteins and neurotransmitters are examples of large molecules that can be transported out of the cell. Exocytosis ...

. A similar process underlies the pancreatic release of insulin. The effects of serotonin upon vascular smooth

muscle tone In physiology, medicine, and anatomy, muscle tone (residual muscle tension or tonus) is the continuous and passive partial contraction of the muscles, or the muscle's resistance to passive stretch during resting state.O’Sullivan, S. B. (2007) ...

the biological function after which serotonin was originally nameddepend upon the serotonylation of proteins involved in the contractile apparatus of muscle cells.

Nervous system

The neurons of the

are the principal source of 5-HT release in the brain. There are nine raphe nuclei, designated B1–B9, which contain the majority of serotonin-containing neurons (some scientists chose to group the ''nuclei raphes lineares'' into one nucleus), all of which are located along the midline of the

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is conti ...

, and centered on the

reticular formation The reticular formation is a set of interconnected nuclei in the brainstem that spans from the lower end of the medulla oblongata to the upper end of the midbrain. The neurons of the reticular formation make up a complex set of neural networks ...

. Axons from the neurons of the raphe nuclei form a neurotransmitter system reaching almost every part of the central nervous system. Axons of neurons in the lower raphe nuclei terminate in the

cerebellum The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...

and

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...

, while the axons of the higher nuclei spread out in the entire brain. It is the dorsal part of the raphe nucleus that contains neurons projecting to the central nervous system. Serotonin-releasing neurons in this area receive input from a large number of areas, notably from

prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...

, lateral habenula, preoptic area,

substantia nigra The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra a ...

and

amygdala The amygdala (; : amygdalae or amygdalas; also '; Latin from Greek language, Greek, , ', 'almond', 'tonsil') is a paired nucleus (neuroanatomy), nuclear complex present in the Cerebral hemisphere, cerebral hemispheres of vertebrates. It is c ...

. These neurons are thought to communicate the expectation of rewards in the near future, a quantity called state value in

reinforcement learning Reinforcement learning (RL) is an interdisciplinary area of machine learning and optimal control concerned with how an intelligent agent should take actions in a dynamic environment in order to maximize a reward signal. Reinforcement learnin ...

Ultrastructure and function

The serotonin nuclei may also be divided into two main groups, the rostral and caudal containing three and four nuclei respectively. The rostral group consists of the caudal linear nuclei (B8), the dorsal raphe nuclei (B6 and B7) and the median raphe nuclei (B5, B8 and B9), that project into multiple cortical and subcortical structures. The caudal group consists of the nucleus raphe magnus (B3), raphe obscurus nucleus (B2), raphe pallidus nucleus (B1), and lateral medullary reticular formation, that project into the brainstem. The serotonergic pathway is involved in sensorimotor function, with pathways projecting both into cortical (Dorsal and Median Raphe Nuclei), subcortical, and spinal areas involved in motor activity. Pharmacological manipulation suggests that serotonergic activity increases with motor activity while firing rates of serotonergic neurons increase with intense visual stimuli. Animal models suggest that kainate signaling negatively regulates serotonin actions in the retina, with possible implications for the control of the visual system. The descending projections form a pathway that inhibits pain called the "descending inhibitory pathway" that may be relevant to a disorder such as fibromyalgia, migraine, and other pain disorders, and the efficacy of antidepressants in them. Serotonergic projections from the caudal nuclei are involved in regulating mood and emotion, and hypo- or hyper-serotonergic states may be involved in depression and sickness behavior.

Microanatomy

Serotonin is released into the synapse, or space between neurons, and diffuses over a relatively wide gap (>20 nm) to activate

5-HT receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the Central nervous system, central and peripheral nervous systems ...

s located on the

dendrite A dendrite (from Ancient Greek language, Greek δένδρον ''déndron'', "tree") or dendron is a branched cytoplasmic process that extends from a nerve cell that propagates the neurotransmission, electrochemical stimulation received from oth ...

s, cell bodies, and presynaptic terminals of adjacent neurons. When humans smell food, dopamine is released to increase the appetite. But, unlike in worms, serotonin does not increase anticipatory behaviour in humans; instead, the serotonin released while consuming activates

5-HT2C receptor The 5-HT2C receptor is a subtype of the 5-HT2 receptor that binds the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Like all 5-HT2 receptors, it is a G protein-coupled receptor (GPCR) that is coupled to Gq/G11 and mediat ...

s on dopamine-producing cells. This halts their dopamine release, and thereby serotonin decreases appetite. Drugs that block 5-HT_2C receptors make the body unable to recognize when it is no longer hungry or otherwise in need of nutrients, and are associated with weight gain, especially in people with a low number of receptors. The expression of 5-HT_2C receptors in the

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

follows a diurnal rhythm, just as the serotonin release in the

ventromedial nucleus The ventromedial nucleus of the hypothalamus (VMN, VMH or ventromedial hypothalamus) is a nucleus of the hypothalamus. In 2007, Kurrasch ''et al''. found that the ventromedial hypothalamus is a distinct morphological nucleus involved in termina ...

, which is characterised by a peak at morning when the motivation to eat is strongest. In

macaque The macaques () constitute a genus (''Macaca'') of gregarious Old World monkeys of the subfamily Cercopithecinae. The 23 species of macaques inhabit ranges throughout Asia, North Africa, and Europe (in Gibraltar). Macaques are principally f ...

s, alpha males have twice the level of serotonin in the brain as subordinate males and females (measured by the concentration of 5-HIAA in the

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...

(CSF)). Dominance status and CSF serotonin levels appear to be positively correlated. When dominant males were removed from such groups, subordinate males begin competing for dominance. Once new dominance hierarchies were established, serotonin levels of the new dominant individuals also increased to double those in subordinate males and females. The reason why serotonin levels are only high in dominant males, but not dominant females has not yet been established. In humans, levels of 5-HT_1A receptor inhibition in the brain show negative correlation with aggression, and a mutation in the gene that codes for the 5-HT_2A receptor may double the risk of suicide for those with that genotype. Serotonin in the brain is not usually degraded after use, but is collected by serotonergic neurons by

serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein t ...

s on their cell surfaces. Studies have revealed nearly 10% of total variance in anxiety-related personality depends on variations in the description of where, when and how many serotonin transporters the neurons should deploy.

Outside the nervous system

Digestive tract (emetic)

Serotonin regulates gastrointestinal (GI) function. The gut is surrounded by

s, which release serotonin in response to food in the lumen. This makes the gut contract around the food. Platelets in the veins draining the gut collect excess serotonin. There are often serotonin abnormalities in gastrointestinal disorders such as constipation and irritable bowel syndrome. If irritants are present in the food, the enterochromaffin cells release more serotonin to make the gut move faster, i.e., to cause diarrhea, so the gut is emptied of the noxious substance. If serotonin is released in the blood faster than the platelets can absorb it, the level of free serotonin in the blood is increased. This activates

5-HT3 receptor The 5-HT3 receptor belongs to the Cys-loop superfamily of ligand-gated ion channels (LGICs) and therefore differs structurally and functionally from all other 5-HT receptors (5-hydroxytryptamine, or serotonin receptors) which are G-protein-coupled ...

s in the chemoreceptor trigger zone that stimulate

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

. Thus, drugs and toxins stimulate serotonin release from enterochromaffin cells in the gut wall can induce emesis. The enterochromaffin cells not only react to bad food but are also very sensitive to

irradiation Irradiation is the process by which an object is exposed to radiation. An irradiator is a device used to expose an object to radiation, most often gamma radiation, for a variety of purposes. Irradiators may be used for sterilizing medical and p ...

and cancer chemotherapy. Drugs that block 5HT3 are very effective in controlling the nausea and vomiting produced by cancer treatment, and are considered the gold standard for this purpose.

Lungs

The

lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...

, including that of reptiles, contains specialized

epithelial cells Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

that occur as solitary cells or as clusters called neuroepithelial bodies or bronchial Kulchitsky cells or alternatively ''K cells''. These are enterochromaffin cells that like those in the gut release serotonin. Their function is probably vasoconstriction during hypoxia.

Skin

Serotonin is also produced by

Merkel cell Merkel cells, also known as Merkel–Ranvier cells or tactile epithelial cells, are oval-shaped mechanoreceptors essential for light touch sensation and found in the skin of vertebrates. They are abundant in highly sensitive skin like that of th ...

s which are part of the

somatosensory The somatosensory system, or somatic sensory system is a subset of the sensory nervous system. The main functions of the somatosensory system are the perception of external stimuli, the perception of internal stimuli, and the regulation of bod ...

system.

Bone metabolism

In mice and humans, alterations in serotonin levels and signalling have been shown to regulate bone mass. Mice that lack brain serotonin have

osteopenia Osteopenia, known as "low bone mass" or "low bone density", is a condition in which bone mineral density is low. Because their bones are weaker, people with osteopenia may have a higher risk of fractures, and some people may go on to develop o ...

, while mice that lack gut serotonin have high bone density. In humans, increased blood serotonin levels have been shown to be a significant negative predictor of low bone density. Serotonin can also be synthesized, albeit at very low levels, in the bone cells. It mediates its actions on bone cells using three different receptors. Through 5-HT_1B receptors, it negatively regulates bone mass, while it does so positively through 5-HT_2B receptors and 5-HT_2C receptors. There is very delicate balance between physiological role of gut serotonin and its pathology. Increase in the extracellular content of serotonin results in a complex relay of signals in the osteoblasts culminating in FoxO1/ Creb and ATF4 dependent transcriptional events. Following the 2008 findings that gut serotonin regulates bone mass, the mechanistic investigations into what regulates serotonin synthesis from the gut in the regulation of bone mass have started. Piezo1 has been shown to sense RNA in the gut and relay this information through serotonin synthesis to the bone by acting as a sensor of single-stranded RNA (ssRNA) governing 5-HT production. Intestinal epithelium-specific deletion of mouse ''Piezo1'' profoundly disturbed gut peristalsis, impeded experimental colitis, and suppressed serum 5-HT levels. Because of systemic 5-HT deficiency, conditional knockout of ''Piezo1'' increased bone formation. Notably, fecal ssRNA was identified as a natural Piezo1 ligand, and ssRNA-stimulated 5-HT synthesis from the gut was evoked in a MyD88/TRIF-independent manner. Colonic infusion of RNase A suppressed gut motility and increased bone mass. These findings suggest gut ssRNA as a master determinant of systemic 5-HT levels, indicating the ssRNA-Piezo1 axis as a potential prophylactic target for treatment of bone and gut disorders. Studies in 2008, 2010 and 2019 have opened the potential for serotonin research to treat bone mass disorders.

Organ development

Since serotonin signals resource availability it is not surprising that it affects organ development. Many human and animal studies have shown that nutrition in early life can influence, in adulthood, such things as body fatness, blood lipids, blood pressure,

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...

, behavior, learning, and longevity. Rodent experiment shows that neonatal exposure to SSRIs makes persistent changes in the serotonergic transmission of the brain resulting in behavioral changes, which are reversed by treatment with antidepressants. By treating normal and

knockout mice A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

lacking the serotonin transporter with fluoxetine scientists showed that normal emotional reactions in adulthood, like a short latency to escape foot shocks and inclination to explore new environments were dependent on active serotonin transporters during the neonatal period. Human serotonin can also act as a

growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for ...

directly. Liver damage increases cellular expression of 5-HT_2A and 5-HT_2B receptors, mediating liver compensatory regrowth (see ) Serotonin present in the blood then stimulates cellular growth to repair liver damage. 5-HT_2B receptors also activate

osteocyte An osteocyte, an oblate-shaped type of bone cell with dendritic processes, is the most commonly found cell in mature bone. It can live as long as the organism itself. The adult human body has about 42 billion of them. Osteocytes do not divide an ...

s, which build up bone However, serotonin also inhibits

osteoblast Osteoblasts (from the Greek combining forms for " bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts fu ...

s, through 5-HT_1B receptors. *

Cardiovascular growth factor

Serotonin, in addition, evokes

endothelial The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the res ...

nitric oxide synthase activation and stimulates, through a

5-HT1B receptor 5-hydroxytryptamine receptor 1B also known as the 5-HT1B receptor is a protein that in humans is encoded by the ''HTR1B'' gene. The 5-HT1B receptor is a 5-HT receptor subtype. Tissue distribution and function 5-HT1B receptors are widely distr ...

-mediated mechanism, the phosphorylation of p44/p42 mitogen-activated protein kinase activation in bovine aortic endothelial cell cultures. In blood, serotonin is collected from plasma by platelets, which store it. It is thus active wherever platelets bind in damaged tissue, as a vasoconstrictor to stop bleeding, and also as a fibrocyte mitotic (growth factor), to aid healing.

Adipose tissue

Serotonin also regulates white and brown adipose tissue function, and adipocytes are capable of producing 5-HT separately from the gut. Serotonin increases lipogenesis through HTR2A in white adipose tissue, and suppressed thermogenesis in brown adipose tissue via Htr3.

Pharmacology

Several classes of

drugs A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via inhalation, injection, smoking, ingestio ...

target the serotonin system, including some

anxiolytic An anxiolytic (; also antipanic or anti-anxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...

analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

s, antimigraine drugs, oxytocics,

antiemetic An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They may ...

appetite suppressant An anorectic is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desi ...

s, and

anticonvulsant Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatme ...

s, as well as psychedelics and

entactogen Entactogens, also known as empathogens or connectogens, are a class of psychoactive drugs that induce the production of experiences of emotional communion, oneness, connectedness, emotional openness—that is, empathy—as particularly observe ...

Mechanism of action

At rest, serotonin is stored within the vesicles of presynaptic neurons. When stimulated by nerve impulses, serotonin is released as a neurotransmitter into the synapse, reversibly binding to the postsynaptic receptor to induce a nerve impulse on the postsynaptic neuron. Serotonin can also bind to auto-receptors on the presynaptic neuron to regulate the synthesis and release of serotonin. Normally serotonin is taken back into the presynaptic neuron to stop its action, then reused or broken down by monoamine oxidase.

Antidepressants

Drugs that alter serotonin levels are used in treating depression,

generalized anxiety disorder Generalized anxiety disorder (GAD) is an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily functioning. Individuals with GAD are often overly con ...

, and

social phobia Social anxiety disorder (SAD), also known as social phobia, is an anxiety disorder characterized by sentiments of fear and anxiety in social situations, causing considerable distress and impairing ability to function in at least some as ...

Monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a drug class, class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressa ...

s (MAOIs) prevent the breakdown of

s (including serotonin), and therefore increase concentrations of the neurotransmitter in the brain. MAOI therapy is associated with many adverse drug reactions, and patients are at risk of hypertensive emergency triggered by foods with high

tyramine Tyramine ( ) (also spelled tyramin), also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the bl ...

content, and certain drugs. Some drugs inhibit the re-uptake of serotonin, making it stay in the synaptic cleft longer. The

(TCAs) inhibit the reuptake of both serotonin and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

. The newer selective serotonin reuptake inhibitors (

SSRI Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by ...

s) have fewer side-effects and fewer interactions with other drugs. Certain SSRI medications have been shown to lower serotonin levels below the baseline after chronic use, despite initial increases. The ''

5-HTTLPR 5-HTTLPR (serotonin-transporter-linked promoter region) is a degenerate repeat (redundancy in the genetic code) polymorphic region in '' SLC6A4'', the gene that codes for the serotonin transporter. Since the polymorphism was identified in th ...

'' gene codes for the number of serotonin transporters in the brain, with more serotonin transporters causing decreased duration and magnitude of serotonergic signaling. The 5-HTTLPR polymorphism (l/l) causing more serotonin transporters to be formed is also found to be more resilient against depression and anxiety. Besides their use in treating depression and anxiety, certain serotonergic antidepressants are also approved and used to treat

fibromyalgia Fibromyalgia (FM) is a functional somatic syndrome with symptoms of widespread chronic pain, accompanied by fatigue, sleep disturbance including awakening unrefreshed, and Cognitive deficit, cognitive symptoms. Other symptoms can include he ...

neuropathic pain Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuo ...

, and

chronic fatigue syndrome Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling Chronic condition, chronic illness. People with ME/CFS experience profound fatigue that does not go away with rest, as well as sleep issues and problems with memory ...

Anxiolytics

Azapirone Azapirones are a class of drugs used as anxiolytics, antidepressants, and antipsychotics. They are commonly used as Augmentation (psychiatry), add-ons to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). List of ...

s like

buspirone Buspirone, sold under the brand name Buspar among others, is an anxiolytic, a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder (GAD). It is a serotonin 5-HT1A receptor, 5-HT1A receptor partial ag ...

and tandospirone act as serotonin 5-HT_1A receptor

Antipsychotics

Many

s bind to and modulate

s, including the serotonin 5-HT_1A, 5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT₆, and 5-HT₇ receptors, among others. Activation of serotonin 5-HT_1A receptors and blockade of serotonin 5-HT_2A receptors may contribute to the therapeutic antipsychotic effects of these agents, whereas antagonism of serotonin 5-HT_2C receptors has been especially implicated in

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of antipsychotics.

Antimigraine agents

Antimigraine agents such as the

triptan Triptans are a family of tryptamine-based medication, drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first commercially introduced in the 1990s. While effective at treating individual h ...

s like

sumatriptan Sumatriptan, sold under the brand name Imitrex among others, is a medication used to treat migraine headaches and cluster headaches. It is taken Oral administration, orally, Nasal administration, intranasally, or by Subcutaneous injection, su ...

act as

s of the serotonin 5-HT_1B, 5-HT_1D, and/or 5-HT_1F receptors. Earlier antimigraine agents were the

ergoline Ergoline is a core structure in many alkaloids and their synthetic derivatives. Ergoline alkaloids were first characterized in ergot. Some of these are implicated in the condition of ergotism, which can take a convulsive form or a gangrenous for ...

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

s and

ergot Ergot ( ) or ergot fungi refers to a group of fungi of the genus ''Claviceps''. The most prominent member of this group is '' Claviceps purpurea'' ("rye ergot fungus"). This fungus grows on rye and related plants, and produces alkaloids that c ...

-related drugs such as

ergotamine Ergotamine, sold under the brand name Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It is structurally similar to several neurotransmitter ...

, dihydroergotamine, and methysergide, which act as non-selective

serotonin receptor agonist A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin (5-hydroxytryptamine; 5-HT), a neurotransmitter and hormone and the endogenous ligand of t ...

Oxytocics

Certain lysergamides like ergometrine and

methylergometrine Methylergometrine, also known as methylergonovine and sold under the brand name Methergine, is a medication of the ergoline and lysergamide groups which is used as an oxytocic in obstetrics and as an antimigraine agent in the treatment of mi ...

are used clinically as oxytocic agents. The oxytocic effects of these drugs are thought to most likely be mediated by

agonism Agonism (from Greek 'struggle') is a political and social theory that emphasizes the potentially positive aspects of certain forms of conflict. It accepts a permanent place for such conflict in the political sphere, but seeks to show how indivi ...

of serotonin 5-HT₂ receptors in uterine

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

tissue.

Antiemetics

Some serotonin 5-HT₃ receptor antagonists, such as

ondansetron Ondansetron, sold under the brand name Zofran among others, is a medication used to prevent nausea and vomiting caused by chemotherapy, radiation therapy, migraines, or surgery. It is also effective for treating gastroenteritis. It can be giv ...

granisetron Granisetron is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy and radiotherapy. Its main effect is to reduce the activity of the vagus nerve, which is a nerve that activates the ...

, and

tropisetron Tropisetron is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic to treat nausea and vomiting following chemotherapy, although it has been used experimentally as an analgesic in cases of fibromyalgia. It was patented in 198 ...

, are important

agents. They are particularly important in treating the

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

and

that occur during anticancer chemotherapy using cytotoxic drugs. Another application is in the treatment of

postoperative nausea and vomiting Postoperative nausea and vomiting (PONV) is the common complication of nausea, vomiting, or retching experienced by a person within the first 24 hours following a surgical procedure. Untreated, PONV affects about 30% of people undergoing general an ...

Appetite suppressants

Some serotonin releasing agents,

serotonin reuptake inhibitor A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the drug action, action of the serotonin transporter (SERT). This in turn lea ...

s, and/or serotonin 5-HT_2C receptor

s, such as

fenfluramine Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome. It was formerly used as an appetite suppressant in the treat ...

dexfenfluramine Dexfenfluramine, formerly sold under the brand name Redux, is a Serotonin, serotonergic drug that was used as an appetite suppressant to promote weight loss. It is the d-enantiomer of fenfluramine and is structurally similar to amphetamine, but ...

, chlorphentermine, sibutramine, and

lorcaserin Lorcaserin, marketed under the brand name Belviq, was a weight-loss drug developed by Arena Pharmaceuticals. It reduces appetite by activating serotonin receptor the 5-HT2C receptor in the hypothalamus, a region of the brain which is known to ...

, have been approved and used as

s for purposes of

weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...

in the treatment of overweightness or

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

. Several of the preceding agents have been withdrawn from the market due to

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect o ...

, such as cardiac fibrosis or

pulmonary hypertension Pulmonary hypertension (PH or PHTN) is a condition of increased blood pressure in the pulmonary artery, arteries of the lungs. Symptoms include dypsnea, shortness of breath, Syncope (medicine), fainting, tiredness, chest pain, pedal edema, swell ...

Anticonvulsants

Although it was previously withdrawn from the market as an appetite suppressant, fenfluramine was reintroduced as an

for treatment of

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

s in certain rare forms of

epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

Dravet syndrome Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy (SMEI), is an autosomal dominant genetic disorder which causes a catastrophic form of epilepsy, with prolonged seizures that are often triggered by hot temperatures o ...

and Lennox–Gastaut syndrome. Selective serotonin 5-HT_2C receptor agonists, like lorcaserin, bexicaserin, and BMB-101, are also being developed for this use.

Psychedelics

Serotonergic psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

s, including drugs like

psilocybin Psilocybin, also known as 4-phosphoryloxy-''N'',''N''-dimethyltryptamine (4-PO-DMT), is a natural product, naturally occurring tryptamine alkaloid and Investigational New Drug, investigational drug found in more than List of psilocybin mushroom ...

(found in

psilocybin mushroom Psilocybin mushrooms, or psilocybin-containing mushrooms, commonly known as magic mushrooms or as shrooms, are a type of hallucinogenic mushroom and a polyphyletic informal group of fungi that contain the prodrug psilocybin, which turns into t ...

s),

dimethyltryptamine Dimethyltryptamine (DMT), also known as ''N'',''N''-dimethyltryptamine (''N'',''N''-DMT), is a Psychedelic drug, serotonergic hallucinogen and Investigational New Drug, investigational drug of the substituted tryptamine, tryptamine family tha ...

(DMT) (found in

ayahuasca AyahuascaPronounced as in the UK and in the US. Also occasionally known in English as ''ayaguasca'' (Spanish-derived), ''aioasca'' (Brazilian Portuguese-derived), or as ''yagé'', pronounced or . Etymologically, all forms but ''yagé'' descen ...

lysergic acid diethylamide Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a Semisynthesis, semisynthetic, Hallucinogen, hallucinogenic compound derived from ergot, known for its powerful psychological effects and ...

(LSD),

mescaline Mescaline, also known as mescalin or mezcalin, and in chemical terms 3,4,5-trimethoxyphenethylamine, is a natural product, naturally occurring psychedelic drug, psychedelic alkaloid, protoalkaloid of the substituted phenethylamine class, found ...

(found in peyote cactus), and

5-MeO-DMT 5-MeO-DMT (5-methoxy-''N'',''N''-dimethyltryptamine), also known as ''O''-methylbufotenin or mebufotenin (), is a naturally occurring psychedelic of the tryptamine family. It is found in a wide variety of plant species, and is also secreted by ...

(found in ''

Anadenanthera ''Anadenanthera'' is a genus of South American trees in the Legume family, Fabaceae. The genus contains two species, ''Anadenanthera colubrina, A. colubrina'' and ''Anadenanthera peregrina, A. peregrina''. These trees are known to the western wor ...

'' trees and the '' Bufo alvarius'' toad), are non-selective

s of the

s and mediate their

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, mo ...

ic effects specifically by activation of the serotonin 5-HT_2A receptor. This is evidenced by the fact that serotonin 5-HT_2A receptor antagonists and so-called " trip killers" like

ketanserin Ketanserin, sold under the brand name Sufrexal, is an antihypertensive agent which is used to treat arterial hypertension and vasospasm, vasospastic disorders. It is also used in scientific research as an antiserotonergic medication, agent in th ...

block the hallucinogenic effects of serotonergic psychedelics in humans, among many other findings. Some serotonergic psychedelics, like

psilocin Psilocin, also known as 4-hydroxy-''N'',''N''-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocy ...

, DMT, and 5-MeO-DMT, are

substituted tryptamine Substituted tryptamines, or simply tryptamines, also known as serotonin analogues (i.e., 5-hydroxytryptamine analogues), are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all trypt ...

s and are very similar in

chemical structure A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target m ...

to serotonin. Serotonin itself, despite acting as a serotonin 5-HT_2A receptor agonist, is thought to be non-hallucinogenic. The hallucinogenic effects of serotonergic psychedelics appear to be mediated by activation of serotonin 5-HT_2A receptors expressed in a population of cortical

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s in the

medial prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA ...

(mPFC). These serotonin 5-HT_2A receptors, unlike most serotonin and related receptors, are expressed

ly. In addition, the neurons containing them lack expression of the

(SERT), which normally

transport Transport (in British English) or transportation (in American English) is the intentional Motion, movement of humans, animals, and cargo, goods from one location to another. Mode of transport, Modes of transport include aviation, air, land tr ...

s serotonin from the

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

space to the intracellular space within neurons. Serotonin itself is too

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...

to enter serotonergic neurons without the SERT, and hence these serotonin 5-HT_2A receptors are inaccessible to serotonin. Conversely, serotonergic psychedelics are more

lipophilic Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...

than serotonin and readily enter these neurons. In addition to explaining why serotonin does not show psychedelic effects, these findings may explain why drugs that increase serotonin levels, like

s (SSRIs) and various other types of serotonergic agents, do not produce psychedelic effects. Artificial expression of the SERT in these medial prefrontal cortex neurons resulted in the serotonin releasing agent ''para''-chloroamphetamine (PCA), which does not normally show psychedelic-like effects, being able to produce psychedelic-like effects in animals. Although serotonin itself is non-hallucinogenic, administration of very high doses of a serotonin precursor, like

or 5-hydroxytryptophan (5-HTP), or intracerebroventricular injection of high doses of serotonin directly into the brain, can produce psychedelic-like effects in animals. These psychedelic-like effects can be abolished by indolethylamine ''N''-methyltransferase (INMT)

inhibitor Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...

s, which block conversion of serotonin and other endogenous tryptamines into ''N''-

methylated Methylation, in the chemical sciences, is the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These term ...

tryptamines, including ''N''-methylserotonin (NMS; norbufotenin),

bufotenin Bufotenin, also known as dimethylserotonin or as 5-hydroxy-''N'',''N''-dimethyltryptamine (5-HO-DMT), is a serotonergic psychedelic of the tryptamine family. It is a derivative of the psychedelic dimethyltryptamine (DMT) and of the neurotransmi ...

(5-hydroxy-''N'',''N''-dimethyltryptamine; 5-HO-DMT), ''N''-methyltryptamine (NMT), and ''N'',''N''-dimethyltryptamine (DMT). These ''N''-methyltryptamines are much more lipophilic than serotonin and, in contrast, are able to

diffuse Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...

into serotonergic neurons and activate intracellular serotonin 5-HT_2A receptors. Another possible metabolite of serotonin with psychedelic-like effects in animals is 5-methoxytryptamine (5-MT). DMT is a

naturally occurring A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical ...

compound in the body. In relation to the fact that serotonin itself is unable to activate intracellular serotonin 5-HT_2A receptors, it is possible that DMT might be the endogenous

of these receptors rather than serotonin.

Entactogens

The

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with stimulant and minor Psychedelic drug, psychedelic properties. In studies, it has been used ...

is a serotonin releasing agent and, while it also possesses other actions such as concomitant release of norepinephrine and

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

and weak direct

of the serotonin 5-HT₂ receptors, its serotonin release plays a key role in its unique entactogenic effects. Entactogens like MDMA should be distinguished from other drugs such as

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

s like

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

and psychedelics like

LSD Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a semisynthetic, hallucinogenic compound derived from ergot, known for its powerful psychological effects and serotonergic activity. I ...

, although MDMA itself also has some characteristics of both of these types of agents. Coadministration of

s (SSRIs), which block the

(SERT) and prevent MDMA from inducing serotonin release, markedly reduce the subjective effects of MDMA, demonstrating the key role of serotonin in the effects of the drug. Serotonin releasing agents like MDMA achieve much greater increases in serotonin levels than SSRIs and have far more robust of subjective effects. Besides MDMA, many other entactogens also exist and are known.

Serotonin syndrome

Extremely high levels of serotonin or activation of certain serotonin receptors can cause a condition known as

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain Serotonin, serotonergic medications or Recreational drug use, drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild c ...

, with toxic and potentially fatal effects. In practice, such toxic levels are essentially impossible to reach through an

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014.

of a single antidepressant drug, but require a combination of serotonergic agents, such as an

with a

MAOI Monoamine oxidase inhibitors (MAOIs) are a drug class, class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressa ...

, which may occur in therapeutic doses. However, serotonin syndrome can occur with overdose of certain serotonin receptor agonists, like the

NBOMe The 25-NB (25''x''-NB''x'') series, or NBOMe series, also known as the ''N''-benzylphenethylamines, is a family of serotonergic psychedelics. They are substituted phenethylamines and were derived from the 2C (psychedelics), 2C family. The most c ...

series of serotonergic psychedelics. The intensity of the symptoms of serotonin syndrome vary over a wide spectrum, and the milder forms are seen even at nontoxic levels. It is estimated that 14% of patients experiencing serotonin syndrome overdose on SSRIs; meanwhile the fatality rate is between 2% and 12%.

Cardiac fibrosis and other fibroses

Some serotonergic agonist drugs cause fibrosis anywhere in the body, particularly the syndrome of

retroperitoneal fibrosis Retroperitoneal fibrosis or Ormond's disease is a disease featuring the proliferation of fibrous tissue (fibrosis) in the retroperitoneum, the compartment of the body containing the kidneys, aorta, renal tract, and various other structures. It m ...

, as well as cardiac valve fibrosis. In the past, three groups of serotonergic drugs have been epidemiologically linked with these syndromes. These are the serotonergic vasoconstrictive antimigraine drugs (

and methysergide), the serotonergic appetite suppressant drugs (

, chlorphentermine, and aminorex), and certain anti-Parkinsonian dopaminergic agonists, which also stimulate serotonergic 5-HT_2B receptors. These include pergolide and cabergoline, but not the more dopamine-specific lisuride. As with fenfluramine, some of these drugs have been withdrawn from the market after groups taking them showed a statistical increase of one or more of the side effects described. An example is pergolide. The drug was declining in use since it was reported in 2003 to be associated with cardiac fibrosis. Two independent studies published in ''

The New England Journal of Medicine ''The New England Journal of Medicine'' (''NEJM'') is a weekly medical journal published by the Massachusetts Medical Society. Founded in 1812, the journal is among the most prestigious peer-reviewed medical journals. Its 2023 impact factor w ...

'' in January 2007 implicated pergolide, along with cabergoline, in causing

valvular heart disease Valvular heart disease is any cardiovascular disease process involving one or more of the four valves of the heart (the aortic and mitral valves on the left side of heart and the pulmonic and tricuspid valves on the right side of heart). The ...

. As a result of this, the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

removed pergolide from the United States market in March 2007. (Since cabergoline is not approved in the United States for Parkinson's Disease, but for hyperprolactinemia, the drug remains on the market. Treatment for hyperprolactinemia requires lower doses than that for Parkinson's Disease, diminishing the risk of valvular heart disease).

Comparative biology and evolution

Unicellular organisms

Serotonin is used by a variety of single-cell organisms for various purposes. SSRIs have been found to be toxic to algae. The gastrointestinal parasite ''

Entamoeba histolytica ''Entamoeba histolytica'' is an anaerobic organism, anaerobic parasitic amoebozoan, part of the genus ''Entamoeba''. Predominantly infecting humans and other primates causing amoebiasis, ''E. histolytica'' is estimated to infect about 35-50 mil ...

'' secretes serotonin, causing a sustained secretory diarrhea in some people. Patients infected with ''E. histolytica'' have been found to have highly elevated serum serotonin levels, which returned to normal following resolution of the infection. ''E. histolytica'' also responds to the presence of serotonin by becoming more virulent. This means serotonin secretion not only serves to increase the spread of entamoebas by giving the host diarrhea but also serves to coordinate their behaviour according to their population density, a phenomenon known as

quorum sensing In biology, quorum sensing or quorum signaling (QS) is the process of cell-to-cell communication that allows bacteria to detect and respond to cell population density by gene regulation, typically as a means of acclimating to environmental disadv ...

. Outside the gut of a host, there is nothing that the entamoebas provoke to release serotonin, hence the serotonin concentration is very low. Low serotonin signals to the entamoebas they are outside a host and they become less virulent to conserve energy. When they enter a new host, they multiply in the gut, and become more virulent as the enterochromaffine cells get provoked by them and the serotonin concentration increases.

Edible plants and mushrooms

In drying

seed In botany, a seed is a plant structure containing an embryo and stored nutrients in a protective coat called a ''testa''. More generally, the term "seed" means anything that can be Sowing, sown, which may include seed and husk or tuber. Seeds ...

s, serotonin production is a way to get rid of the buildup of poisonous

ammonia Ammonia is an inorganic chemical compound of nitrogen and hydrogen with the chemical formula, formula . A Binary compounds of hydrogen, stable binary hydride and the simplest pnictogen hydride, ammonia is a colourless gas with a distinctive pu ...

. The ammonia is collected and placed in the

part of L-

, which is then decarboxylated by tryptophan decarboxylase to give tryptamine, which is then hydroxylated by a

cytochrome P450 monooxygenase Cytochromes P450 (P450s or CYPs) are a superfamily of enzymes containing heme as a cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for example, they have not been found in ''Escherichi ...

, yielding serotonin. However, since serotonin is a major gastrointestinal tract modulator, it may be produced in the fruits of plants as a way of speeding the passage of seeds through the digestive tract, in the same way as many well-known seed and fruit associated laxatives. Serotonin is found in

mushrooms A mushroom or toadstool is the fleshy, spore-bearing fruiting body of a fungus, typically produced above ground on soil or another food source. ''Toadstool'' generally refers to a poisonous mushroom. The standard for the name "mushroom" is ...

fruit In botany, a fruit is the seed-bearing structure in flowering plants (angiosperms) that is formed from the ovary after flowering. Fruits are the means by which angiosperms disseminate their seeds. Edible fruits in particular have long propaga ...

s, and

vegetable Vegetables are edible parts of plants that are consumed by humans or other animals as food. This original meaning is still commonly used, and is applied to plants collectively to refer to all edible plant matter, including edible flower, flo ...

s. The highest values of 25–400 mg/kg have been found in nuts of the

walnut A walnut is the edible seed of any tree of the genus '' Juglans'' (family Juglandaceae), particularly the Persian or English walnut, '' Juglans regia''. They are accessory fruit because the outer covering of the fruit is technically an i ...

(''Juglans'') and

hickory Hickory is a common name for trees composing the genus ''Carya'', which includes 19 species accepted by ''Plants of the World Online''. Seven species are native to southeast Asia in China, Indochina, and northeastern India (Assam), and twelve ...

(''Carya'') genera. Serotonin concentrations of 3–30 mg/kg have been found in plantains,

pineapple The pineapple (''Ananas comosus'') is a Tropical vegetation, tropical plant with an edible fruit; it is the most economically significant plant in the family Bromeliaceae. The pineapple is indigenous to South America, where it has been culti ...

banana A banana is an elongated, edible fruit – botanically a berry – produced by several kinds of large treelike herbaceous flowering plants in the genus '' Musa''. In some countries, cooking bananas are called plantains, distinguishing the ...

kiwifruit Kiwifruit (often shortened to kiwi), or Chinese gooseberry, is the edible berry (botany), berry of several species of woody vines in the genus ''Actinidia''. The most common cultivar group of kiwifruit (Actinidia chinensis var. deliciosa, ...

plum A plum is a fruit of some species in Prunus subg. Prunus, ''Prunus'' subg. ''Prunus'.'' Dried plums are often called prunes, though in the United States they may be labeled as 'dried plums', especially during the 21st century. Plums are ...

s, and

tomato The tomato (, ), ''Solanum lycopersicum'', is a plant whose fruit is an edible Berry (botany), berry that is eaten as a vegetable. The tomato is a member of the nightshade family that includes tobacco, potato, and chili peppers. It originate ...

es. Moderate levels from 0.1–3 mg/kg have been found in a wide range of tested vegetables. Serotonin is one compound of the poison contained in

stinging nettle ''Urtica dioica'', often known as common nettle, burn nettle, stinging nettle (although not all plants of this species sting) or nettle leaf, or just a nettle or stinger, is a herbaceous perennial flowering plant in the family Urticaceae. Or ...

s (''Urtica dioica''), where it causes pain on injection in the same manner as its presence in insect venoms. It is also naturally found in ''

Paramuricea clavata ''Paramuricea clavata'', the violescent sea-whip, is a species of Colony (biology), colonial soft coral in the Family (biology), family Plexauridae. It is found in shallow seas of the north-eastern Atlantic Ocean and the north-western Mediterrane ...

'', or the Red Sea Fan. Serotonin and tryptophan have been found in chocolate with varying cocoa contents. The highest serotonin content (2.93 μg/g) was found in chocolate with 85% cocoa, and the highest tryptophan content (13.27–13.34 μg/g) was found in 70–85% cocoa. The intermediate in the synthesis from tryptophan to serotonin, 5-hydroxytryptophan, was not found. Root development in ''

Arabidopsis thaliana ''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small plant from the mustard family (Brassicaceae), native to Eurasia and Africa. Commonly found along the shoulders of roads and in disturbed land, it is generally ...

'' is stimulated and modulated by serotonin – in various ways at various concentrations. Serotonin serves as a plant defense chemical against fungi. When infected with Fusarium crown rot (''Fusarium pseudograminearum''),

wheat Wheat is a group of wild and crop domestication, domesticated Poaceae, grasses of the genus ''Triticum'' (). They are Agriculture, cultivated for their cereal grains, which are staple foods around the world. Well-known Taxonomy of wheat, whe ...

(''Triticum aestivum'') greatly increases its production of tryptophan to synthesize new serotonin. The function of this is poorly understood but wheat also produces serotonin when infected by '' Stagonospora nodorum'' – in that case to retard spore production. The model

cereal A cereal is a grass cultivated for its edible grain. Cereals are the world's largest crops, and are therefore staple foods. They include rice, wheat, rye, oats, barley, millet, and maize ( Corn). Edible grains from other plant families, ...

Brachypodium distachyon ''Brachypodium distachyon'', commonly called purple false brome or stiff brome, is a grass species native to southern Europe, northern Africa and southwestern Asia east to India. It is related to the major cereal grain species wheat, barley, oats ...

'' – used as a research substitute for wheat and other production cereals – also produces serotonin,

coumaroyl Coumaric acid is a phenolic derivative of cinnamic acid having a hydroxy group as substituent at one of the aromatic In organic chemistry, aromaticity is a chemical property describing the way in which a conjugated system, conjugated ring of uns ...

-serotonin, and feruloyl-serotonin in response to '' F. graminearum''. This produces a slight

antimicrobial An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth (bacteriostatic agent). Antimicrobial medicines can be grouped according to the microorganisms they are used to treat. For example, antibiotics are used aga ...

effect. ''B. distachyon'' produces more serotonin (and conjugates) in response to

deoxynivalenol Vomitoxin, also known as deoxynivalenol (DON), is a type B trichothecene, an epoxy- sesquiterpenoid. This mycotoxin occurs predominantly in grains such as wheat, barley, oats, rye, and corn, and less often in rice, sorghum, and triticale. The o ...

(DON)-producing ''F. graminearum'' than non-DON-producing. '' Solanum lycopersicum'' produces many AA conjugates – including several of serotonin – in its leaves, stems, and roots in response to '' Ralstonia solanacearum'' infection. Serotonin occurs in several hallucinogenic mushrooms of the genus '' Panaeolus''.

Invertebrates

Serotonin functions as a neurotransmitter in the nervous systems of most animals.

Nematodes

For example, in the roundworm ''

Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a Hybrid word, blend of the Greek ''caeno-'' (recent), ''r ...

'', which feeds on bacteria, serotonin is released as a signal in response to positive events, such as finding a new source of food or in male animals finding a female with which to mate. When a well-fed worm feels bacteria on its

cuticle A cuticle (), or cuticula, is any of a variety of tough but flexible, non-mineral outer coverings of an organism, or parts of an organism, that provide protection. Various types of "cuticle" are non- homologous, differing in their origin, structu ...

is released, which slows it down; if it is starved, serotonin also is released, which slows the animal down further. This mechanism increases the amount of time animals spend in the presence of food. The released serotonin activates the muscles used for feeding, while octopamine suppresses them. Serotonin diffuses to serotonin-sensitive neurons, which control the animal's perception of nutrient availability.

Decapods

lobster Lobsters are Malacostraca, malacostracans Decapoda, decapod crustaceans of the family (biology), family Nephropidae or its Synonym (taxonomy), synonym Homaridae. They have long bodies with muscular tails and live in crevices or burrows on th ...

s are injected with serotonin, they behave like dominant individuals whereas octopamine causes subordinate behavior. A

crayfish Crayfish are freshwater crustaceans belonging to the infraorder Astacidea, which also contains lobsters. Taxonomically, they are members of the superfamilies Astacoidea and Parastacoidea. They breathe through feather-like gills. Some spe ...

that is frightened may flip its tail to flee, and the effect of serotonin on this behavior depends largely on the animal's social status. Serotonin inhibits the fleeing reaction in subordinates, but enhances it in socially dominant or isolated individuals. The reason for this is social experience alters the proportion between

s (5-HT receptors) that have opposing effects on the

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 describ ...

. The effect of 5-HT₁ receptors predominates in subordinate animals, while 5-HT₂ receptors predominates in dominants.

In venoms

Serotonin is a common component of invertebrate venoms, salivary glands, nervous tissues, and various other tissues, across molluscs, insects, crustaceans, scorpions, various kinds of worms, and jellyfish. Adult '' Rhodnius prolixus'' –

hematophagous Hematophagy (sometimes spelled haematophagy or hematophagia) is the practice by certain animals of feeding on blood (from the Greek words αἷμα ' "blood" and φαγεῖν ' "to eat"). Since blood is a fluid tissue rich in nutritious pr ...

on vertebrates – secrete lipocalins into the wound during feeding. In 2003 these lipocalins were demonstrated to sequester serotonin to prevent vasoconstriction (and possibly coagulation) in the host.

Insects

Serotonin is evolutionarily conserved and appears across the animal kingdom. It is seen in insect processes in roles similar to in the human central nervous system, such as memory, appetite, sleep, and behavior. Some circuits in

mushroom bodies The mushroom bodies or ''corpora pedunculata'' are a pair of structures in the Supraesophageal ganglion, brain of arthropods, including insects and Crustacean, crustaceans, and some annelids (notably the ragworm ''Platynereis dumerilii''). They a ...

are serotonergic. (See specific ''Drosophila'' example below, §Dipterans.)

=Acrididae

= Locust swarming is initiated ''but not maintained'' by serotonin, with release being triggered by tactile contact between individuals. This transforms social preference from aversion to a gregarious state that enables coherent groups. * Learning in flies and honeybees is affected by the presence of serotonin.

=Role in insecticides

= Insect 5-HT receptors have similar sequences to the vertebrate versions, but pharmacological differences have been seen. Invertebrate drug response has been far less characterized than mammalian pharmacology and the potential for species selective insecticides has been discussed.

=Hymenopterans

Wasp A wasp is any insect of the narrow-waisted suborder Apocrita of the order Hymenoptera which is neither a bee nor an ant; this excludes the broad-waisted sawflies (Symphyta), which look somewhat like wasps, but are in a separate suborder ...

s and hornets have serotonin in their venom, which causes pain and inflammation as do

scorpion Scorpions are predatory arachnids of the Order (biology), order Scorpiones. They have eight legs and are easily recognized by a pair of Chela (organ), grasping pincers and a narrow, segmented tail, often carried in a characteristic forward cur ...

s. '' Pheidole dentata'' takes on more and more tasks in the colony as it gets older, which requires it to respond to more and more

olfactory The sense of smell, or olfaction, is the special sense through which smells (or odors) are perceived. The sense of smell has many functions, including detecting desirable foods, hazards, and pheromones, and plays a role in taste. In humans, it ...

cues in the course of performing them. This olfactory response broadening was demonstrated to go along with increased serotonin and

, but not octopamine in 2006.

=Dipterans

= If flies are fed serotonin, they are more aggressive; flies depleted of serotonin still exhibit aggression, but they do so much less frequently. In their crops it plays a vital role in digestive motility produced by contraction. Serotonin that acts on the crop is exogenous to the crop itself and 2012 research suggested that it probably originated in the serotonin neural plexus in the thoracic-abdominal synganglion. In 2011 a ''

Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...

'' serotonergic mushroom body was found to work in concert with '' Amnesiac'' to form memories. In 2007 serotonin was found to promote aggression in ''

Diptera Flies are insects of the order Diptera, the name being derived from the Greek δι- ''di-'' "two", and πτερόν ''pteron'' "wing". Insects of this order use only a single pair of wings to fly, the hindwings having evolved into advance ...

'', which was counteracted by neuropeptide F – a surprising find given that they both promote

courtship Courtship is the period wherein some couples get to know each other prior to a possible marriage or committed romantic, ''de facto'' relationship. Courtship traditionally may begin after a betrothal and may conclude with the celebration of marri ...

, which is usually similar to aggression in most respects.

Vertebrates

Serotonin, also referred to as 5-hydroxytryptamine (5-HT), is a neurotransmitter most known for its involvement in mood disorders in humans. It is also a widely present neuromodulator among vertebrates and invertebrates. Serotonin has been found having associations with many physiological systems such as cardiovascular,

, and behavioral functions, including:

circadian rhythm A circadian rhythm (), or circadian cycle, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism (i.e., Endogeny (biology), endogenous) and responds to the env ...

, appetite, aggressive and sexual behavior, sensorimotor reactivity and learning, and pain sensitivity. Serotonin's function in neurological systems along with specific behaviors among vertebrates found to be strongly associated with serotonin will be further discussed. Two relevant case studies are also mentioned regarding serotonin development involving teleost fish and

mice A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

. In mammals, 5-HT is highly concentrated in the

ventral tegmental area The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is th ...

and

. Lesser concentrated areas include other brain regions and the spinal cord. 5-HT neurons are also shown to be highly branched, indicating that they are structurally prominent for influencing multiple areas of the CNS at the same time, although this trend is exclusive solely to mammals.

5-HT system in vertebrates

Vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

s are multicellular organisms in the phylum Chordata that possess a backbone and a

nervous system In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...

. This includes mammals, fish, reptiles, birds, etc. In humans, the nervous system is composed of the central and

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of Bilateria, bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside t ...

, with little known about the specific mechanisms of neurotransmitters in most other vertebrates. However, it is known that while serotonin is involved in stress and behavioral responses, it is also important in cognitive functions. Brain organization in most vertebrates includes 5-HT cells in the

hindbrain The hindbrain, rhombencephalon (shaped like a rhombus) is a developmental categorization of portions of the central nervous system in vertebrates. It includes the medulla, pons, and cerebellum. Together they support vital bodily processes. Met ...

. In addition to this, 5-HT is often found in other sections of the brain in non-placental vertebrates, including the

basal forebrain Part of the human brain, the basal forebrain structures are located in the forebrain to the front of and below the striatum. They include the ventral basal ganglia (including nucleus accumbens and ventral pallidum), nucleus basalis, diagonal ba ...

and

pretectum In neuroanatomy, the pretectal area, or pretectum, is a midbrain structure composed of seven nuclei and comprises part of the subcortical visual system. Through reciprocal bilateral projections from the retina, it is involved primarily in mediati ...

. Since location of serotonin receptors contribute to behavioral responses, this suggests serotonin is part of specific pathways in non-placental vertebrates that are not present in amniotic organisms. Teleost fish and mice are organisms most often used to study the connection between serotonin and vertebrate behavior. Both organisms show similarities in the effect of serotonin on behavior, but differ in the mechanism in which the responses occur.

=Dogs / canine species

= There are few studies of serotonin in dogs. One study reported serotonin values were higher at dawn than at dusk. In another study, serum 5-HT levels did not seem to be associated with dogs' behavioural response to a stressful situation. Urinary serotonin/creatinine ratio in bitches tended to be higher 4 weeks after surgery. In addition, serotonin was positively correlated with both cortisol and progesterone but not with testosterone after ovariohysterectomy.

=Teleost fish

= Like non-placental vertebrates, teleost fish also possess 5-HT cells in other sections of the brain, including the

. ''

Danio rerio The zebrafish (''Danio rerio'') is a species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (a ...

'' (zebra fish) are a species of teleost fish often used for studying serotonin within the brain. Despite much being unknown about serotonergic systems in vertebrates, the importance in moderating stress and social interaction is known. It is hypothesized that AVT and CRF cooperate with serotonin in th
hypothalamic-pituitary-interrenal axis
These

neuropeptide Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the ...

s influence the plasticity of the teleost, affecting its ability to change and respond to its environment. Subordinate fish in social settings show a drastic increase in 5-HT concentrations. High levels of 5-HT long term influence the inhibition of aggression in subordinate fish.

=Mice

= Researchers at the Department of Pharmacology and Medical Chemistry used serotonergic drugs on male mice to study the effects of selected drugs on their behavior. Mice in isolation exhibit increased levels of agonistic behavior towards one another. Results found that serotonergic drugs reduce aggression in isolated mice while simultaneously increasing social interaction. Each of the treatments use a different mechanism for targeting aggression, but ultimately all have the same outcome. While the study shows that serotonergic drugs successfully target serotonin receptors, it does not show specifics of the mechanisms that affect behavior, as all types of drugs tended to reduce aggression in isolated male mice. Aggressive mice kept out of isolation may respond differently to changes in serotonin reuptake.

Behavior

Like in humans, serotonin is involved in regulating behavior in most other vertebrates. This includes not only response and social behaviors, but also influencing mood. Defects in serotonin pathways can lead to intense variations in mood, as well as symptoms of mood disorders, which can be present in more than just humans.

=Social interaction

= One of the most researched aspects of social interaction in which serotonin is involved is aggression. Aggression is regulated by the 5-HT system, as serotonin levels can both induce or inhibit aggressive behaviors, as seen in mice (see section on Mice) and crabs. While this is widely accepted, it is unknown if serotonin interacts directly or indirectly with parts of the brain influencing aggression and other behaviors. Studies of serotonin levels show that they drastically increase and decrease during social interactions, and they generally correlate with inhibiting or inciting aggressive behavior. The exact mechanism of serotonin influencing social behaviors is unknown, as pathways in the 5-HT system in various vertebrates can differ greatly.

=Response to stimuli

= Serotonin is important in environmental response pathways, along with other

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

s. Specifically, it has been found to be involved in auditory processing in social settings, as primary sensory systems are connected to social interactions. Serotonin is found in the IC structure of the midbrain, which processes specie specific and non-specific social interactions and vocalizations. It also receives acoustic projections that convey signals to auditory processing regions. Research has proposed that serotonin shapes the auditory information being received by the IC and therefore is influential in the responses to auditory stimuli. This can influence how an organism responds to the sounds of predatory or other impactful species in their environment, as serotonin uptake can influence aggression or social interaction.

=Mood

= We can describe mood not as specific to an emotional status, but as associated with a relatively long-lasting emotional state. Serotonin's association with mood is most known for various forms of depression and bipolar disorders in humans. Disorders caused by serotonergic activity potentially contribute to the many symptoms of major depression, such as overall mood, activity, suicidal thoughts and sexual and

cognitive dysfunction Neurocognitive disorders (NCDs), also known as cognitive disorders (CDs), are a category of mental health disorders that primarily affect cognitive abilities including learning, memory, perception, and problem-solving. Neurocognitive disorders in ...

Selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...

s (SSRI's) are a class of drugs demonstrated to be an effective treatment in major depressive disorder and are the most prescribed class of antidepressants. SSRI's function is to block the reuptake of serotonin, making more serotonin available to absorb by the receiving neuron. Animals have been studied for decades in order to understand depressive behavior among species. One of the most familiar studies, the forced swimming test (FST), was performed to measure potential antidepressant activity. Rats were placed in an inescapable container of water, at which point time spent immobile and number of active behaviors (such as splashing or climbing) were compared before and after a panel of anti-depressant drugs were administered. Antidepressants that selectively inhibit NE reuptake were shown to reduce immobility and selectively increase climbing without affecting swimming. However, results of the SSRI's also show reduced immobility but increased swimming without affecting climbing. This study demonstrated the importance of behavioral tests for antidepressants, as they can detect drugs with an effect on core behavior along with behavioral components of species.

Growth and reproduction

In the nematode '' C. elegans'', artificial depletion of serotonin or the increase of octopamine cues behavior typical of a low-food environment: ''C. elegans'' becomes more active, and mating and egg-laying are suppressed, while the opposite occurs if serotonin is increased or octopamine is decreased in this animal. Serotonin is necessary for normal nematode male mating behavior, and the inclination to leave food to search for a mate. The serotonergic signaling used to adapt the worm's behaviour to fast changes in the environment affects

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

-like signaling and the

TGF beta signaling pathway The transforming growth factor beta (TGFβ) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, cell migration, apoptosis, cellular homeostasis a ...

, which control long-term adaption. In the fruit fly insulin both regulates

blood sugar The blood sugar level, blood sugar concentration, blood glucose level, or glycemia is the measure of glucose concentrated in the blood. The body tightly regulates blood glucose levels as a part of metabolic homeostasis. For a 70 kg (1 ...

as well as acting as a

. Thus, in the fruit fly, serotonergic neurons regulate the adult body size by affecting insulin secretion. Serotonin has also been identified as the trigger for swarm behavior in locusts. In humans, though insulin regulates blood sugar and IGF regulates growth, serotonin controls the release of both hormones, modulating insulin release from the

beta cell Beta cells (β-cells) are specialized endocrine cells located within the pancreatic islets of Langerhans responsible for the production and release of insulin and amylin. Constituting ~50–70% of cells in human islets, beta cells play a vi ...

s in the

pancreas The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...

through serotonylation of GTPase signaling proteins. Exposure to

s during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

reduces fetal growth. Genetically altered ''C. elegans'' worms that lack serotonin have an increased reproductive lifespan, may become obese, and sometimes present with arrested development at a dormant larval state.

Aging and age-related phenotypes

Serotonin is known to regulate aging, learning, and memory. The first evidence comes from the study of longevity in ''C. elegans''. During early phase of aging, the level of serotonin increases, which alters locomotory behaviors and associative memory. The effect is restored by mutations and drugs (including mianserin and methiothepin) that inhibit

serotonin receptors 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the Central nervous system, central and peripheral nervous systems ...

. The observation does not contradict with the notion that the serotonin level goes down in mammals and humans, which is typically seen in late but not early phase of aging.

Biochemical mechanisms

Biosynthesis

In animals and humans, serotonin is synthesized from the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

L-

by a short

metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell (biology), cell. The reactants, products, and Metabolic intermediate, intermediates of an enzymatic reaction are known as metabolites, which are ...

consisting of two

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

tryptophan hydroxylase Tryptophan hydroxylase (TPH) is an enzyme () involved in the synthesis of the monoamine neurotransmitter serotonin. Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin-depen ...

(TPH) and aromatic amino acid decarboxylase (DDC), and the coenzyme

pyridoxal phosphate Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependen ...

. The TPH-mediated reaction is the rate-limiting step in the pathway. TPH has been shown to exist in two forms:

TPH1 Tryptophan hydroxylase 1 (TPH1) is an isoenzyme of tryptophan hydroxylase which in humans is encoded by the ''TPH1'' gene. TPH1 was first discovered to support serotonin synthesis in 1988 by converting tryptophan into 5-hydroxytryptophan. It w ...

, found in several tissues, and

TPH2 Tryptophan hydroxylase 2 (TPH2) is an isozyme of tryptophan hydroxylase found in vertebrates. In humans, TPH2 is primarily expressed in the serotonergic neurons of the brain, with the highest expression in the raphe nucleus of the midbrain. Unt ...

, which is a neuron-specific

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

. Serotonin can be synthesized from tryptophan in the lab using ''

Aspergillus niger ''Aspergillus niger'' is a mold classified within the ''Nigri'' section of the ''Aspergillus'' genus. The ''Aspergillus'' genus consists of common molds found throughout the environment within soil and water, on vegetation, in fecal matter, on de ...

'' and '' Psilocybe coprophila'' as catalysts. The first phase to 5-hydroxytryptophan would require letting tryptophan sit in ethanol and water for 7 days, then mixing in enough HCl (or other acid) to bring the pH to 3, and then adding NaOH to make a pH of 13 for 1 hour. ''Aspergillus niger'' would be the catalyst for this first phase. The second phase to synthesizing tryptophan itself from the 5-hydroxytryptophan intermediate would require adding ethanol and water, and letting sit for 30 days this time. The next two steps would be the same as the first phase: adding HCl to make the pH = 3, and then adding NaOH to make the pH very basic at 13 for 1 hour. This phase uses the ''Psilocybe coprophila'' as the catalyst for the reaction. Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system, because it does not cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

. However,

and its

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

5-hydroxytryptophan (5-HTP), from which serotonin is synthesized, do cross the blood–brain barrier. These agents are available as

dietary supplement A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients eithe ...

s and in various foods, and may be effective serotonergic agents. One product of serotonin breakdown is 5-hydroxyindoleacetic acid (5-HIAA), which is excreted in the

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

. Serotonin and 5-HIAA are sometimes produced in excess amounts by certain

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s or

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

s, and levels of these substances may be measured in the urine to test for these tumors.

Analytical chemistry

Indium tin oxide Indium tin oxide (ITO) is a ternary composition of indium, tin and oxygen in varying proportions. Depending on the oxygen content, it can be described as either a ceramic or an alloy. Indium tin oxide is typically encountered as an oxygen-saturate ...

is recommended for the

electrode An electrode is an electrical conductor used to make contact with a nonmetallic part of a circuit (e.g. a semiconductor, an electrolyte, a vacuum or a gas). In electrochemical cells, electrodes are essential parts that can consist of a varie ...

material in

electrochemical Electrochemistry is the branch of physical chemistry concerned with the relationship between electrical potential difference and identifiable chemical change. These reactions involve electrons moving via an electronically conducting phase (typi ...

investigation of concentrations produced, detected, or consumed by

microbe A microorganism, or microbe, is an organism of microscopic size, which may exist in its single-celled form or as a colony of cells. The possible existence of unseen microbial life was suspected from antiquity, with an early attestation in ...

s. A mass spectrometry technique was developed in 1994 to measure the

molecular weight A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...

of both natural and synthetic serotonins.

History and etymology

It had been known to physiologists for over a century that a vasoconstrictor material appears in serum when blood was allowed to clot. In 1935, Italian Vittorio Erspamer, working in Pavia, showed an extract from enterochromaffin cells made intestines contract. Some believed it contained

adrenaline Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

, but two years later, Erspamer was able to show it was a previously unknown

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

, which he named "enteramine". In 1948, Maurice M. Rapport, Arda Green, and Irvine Page of the

Cleveland Clinic Cleveland Clinic is an American Nonprofit organization, nonprofit Academic health science center, academic Medical centers in the United States, medical center based in Cleveland, Ohio. Owned and operated by the Cleveland Clinic Foundation, an O ...

discovered a vasoconstrictor substance in

blood serum Serum () is the fluid and solvent component of blood which does not play a role in clotting. It may be defined as blood plasma without the clotting factors, or as blood with all cells and clotting factors removed. Serum contains all proteins ex ...

, and since it was a serum agent affecting vascular tone, they named it serotonin. In 1952, enteramine was shown to be the same substance as serotonin, and as the broad range of physiological roles was elucidated, the abbreviation 5-HT of the proper chemical name 5-hydroxytryptamine became the preferred name in the pharmacological field. Synonyms of serotonin include: 5-hydroxytriptamine, enteramine, substance DS, and 3-(β-aminoethyl)-5-hydroxyindole. In 1953, Betty Twarog and Page discovered serotonin in the central nervous system. Page regarded Erspamer's work on ''

Octopus vulgaris The common octopus (''Octopus vulgaris'') is a Mollusca, mollusk belonging to the class Cephalopoda. ''Octopus vulgaris'' is one of the most studied of all octopus species, and also one of the most intelligent. It ranges from the eastern Atlanti ...

'', ''

Discoglossus pictus ''Discoglossus pictus'', the Mediterranean painted frog or simply painted frog, is a species of frog in the family Alytidae (formerly Discoglossidae). Distribution ''Discoglossus pictus'' is found Mediterranean Africa in northeast Morocco, nor ...

'', ''

Hexaplex trunculus ''Hexaplex trunculus'' (previously known as ''Murex trunculus'', ''Phyllonotus trunculus'', or the banded dye-murex) is a medium-sized sea snail, a marine gastropod mollusk in the family Muricidae, the murex shells or rock snails. It is inclu ...

'', ''

Bolinus brandaris ''Bolinus brandaris'' (originally called ''Murex brandaris'' by Linnaeus and also Haustellum brandaris), and commonly known as the purple dye murex or the spiny dye-murex, is a species of medium-sized predatory sea snail, an edible marine gastr ...

'', '' Sepia'', '' Mytilus'', and '' Ostrea'' as valid and fundamental to understanding this newly identified substance, but regarded his earlier results in various models – especially those from rat blood – to be too confounded by the presence of other bioactive chemicals, including some other vasoactives.

Effects in humans

Serotonin, given orally at a dose of 100mg, produced effects in humans including

blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

changes, abdominal cramps, muscle aches, and a feeling of

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

. In contrast to psychedelic drugs like

, no

ic effects were reported. In other studies, serotonin, at low

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

doses of 2 to 6mg, had no effects on

electroencephalogram Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The bio signals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neoc ...

(EEG) readings in humans. In accordance with the preceding findings, it has been stated that administration of serotonin in humans produces no

psychoactive A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, psychoactive substance, or psychotropic substance is a chemical substance that alters psychological functioning by modulating central nervous system acti ...

effects that cannot be attributed to

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

by its profound

peripheral A peripheral device, or simply peripheral, is an auxiliary hardware device that a computer uses to transfer information externally. A peripheral is a hardware component that is accessible to and controlled by a computer but is not a core compo ...

adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term compli ...

s including circulatory disturbance, other autonomic effects, and

. Intracerebroventricular injection of serotonin has been studied in patient with severe

psychiatric condition A mental disorder, also referred to as a mental illness, a mental health condition, or a psychiatric disability, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. A mental disorder is ...

s, but little information about its psychoactive effects is provided. It is thought that exogenous serotonin is too

to cross the

and has too poor of metabolic stability due to rapid

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

(MAO) such that it cannot produce

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

-like central effects in humans with peripheral administration. However, close analogues of serotonin that are more

and metabolically stable, like

(''N'',''N''-dimethylserotonin),

(''N'',''N'',''O''-trimethylserotonin), and 5-MeO-AMT (α,''O''-dimethylserotonin), among many others, are active and produce pronounced centrally mediated effects in humans. These drugs are non-selective

s like serotonin and are

s due to activation of the serotonin 5-HT_2A receptor. α-Methylserotonin is well-studied in

preclinical research In drug development, preclinical development (also termed preclinical studies or nonclinical studies) is a stage of research that begins before clinical trials (testing in humans) and during which important feasibility, iterative testing and dr ...

, but is not known to have been tested in humans.

Notes

References

External links

5-Hydroxytryptamine MS Spectrum

Serotonin bound to proteins
in the PDB
PsychoTropicalResearch
Extensive reviews on serotonergic drugs and Serotonin Syndrome.

at

University of Bristol The University of Bristol is a public university, public research university in Bristol, England. It received its royal charter in 1909, although it can trace its roots to a Merchant Venturers' school founded in 1595 and University College, Br ...

* 60-Second Psych
No Fair! My Serotonin Level Is Low

Scientific American ''Scientific American'', informally abbreviated ''SciAm'' or sometimes ''SA'', is an American popular science magazine. Many scientists, including Albert Einstein and Nikola Tesla, have contributed articles to it, with more than 150 Nobel Pri ...

Serotonin Test Interpretation on ClinLab Navigator
. {{Portal bar, Chemistry, Biology, Medicine Biogenic amines Happy hormones 5-Hydroxytryptamines X Neurotransmitters Non-hallucinogenic 5-HT2A receptor agonists Peripherally selective drugs Serotonin receptor agonists Serotonin releasing agents TAAR1 agonists Tryptamine alkaloids Aminoethyl compounds

Molecular structure

Crystal structure

Biological role

Cellular effects

Receptors

Termination

Serotonylation

Nervous system

Ultrastructure and function

Microanatomy

Outside the nervous system

Digestive tract (emetic)

Lungs

Skin

Bone metabolism

Organ development

Cardiovascular growth factor

Adipose tissue

Pharmacology

Mechanism of action

Antidepressants

Anxiolytics

Antipsychotics

Antimigraine agents

Oxytocics

Antiemetics

Appetite suppressants

Anticonvulsants

Psychedelics

Entactogens

Serotonin syndrome

Cardiac fibrosis and other fibroses

Comparative biology and evolution

Unicellular organisms

Edible plants and mushrooms

Invertebrates

Nematodes

Decapods

In venoms

Insects

=Acrididae

=Role in insecticides

=Hymenopterans

=Dipterans

Vertebrates

5-HT system in vertebrates

=Dogs / canine species

=Teleost fish

=Mice

Behavior

=Social interaction

=Response to stimuli

=Mood

Growth and reproduction

Aging and age-related phenotypes

Biochemical mechanisms

Biosynthesis

Analytical chemistry

History and etymology

Effects in humans

Notes

References

Further reading

External links