Vomiting Center
   HOME

TheInfoList



OR:

The area postrema, a paired structure in the
medulla oblongata The medulla oblongata or simply medulla is a long stem-like structure which makes up the lower part of the brainstem. It is anterior and partially inferior to the cerebellum. It is a cone-shaped neuronal mass responsible for autonomic (involun ...
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 ...
, is a
circumventricular organ Circumventricular organs (CVOs) ( circum-: around ; ventricular: of ventricle) are structures in the brain characterized by their extensive and highly permeable capillaries, unlike those in the rest of the brain where there exists a blood–b ...
having
permeable Permeability, permeable, and semipermeable may refer to: Chemistry *Drug permeability *Semipermeable membrane, a membrane which will allow certain molecules or ions to pass through it by diffusion *Vascular permeability, the movement of fluids a ...
capillaries A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima (the in ...
and
sensory neuron Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded receptor potentials. This process is called sensory transduc ...
s that enable its role to detect circulating chemical messengers in the blood and transduce them into neural signals and networks. Its position adjacent to the bilateral nuclei of the solitary tract and role as a sensory transducer allow it to integrate blood-to-brain autonomic functions. Such roles of the area postrema include its detection of circulating
hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
s involved in
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 ...
,
thirst Thirst is the craving for potable fluids, resulting in the basic instinct of animals to drink. It is an essential mechanism involved in fluid balance. It arises from a lack of fluids or an increase in the concentration of certain osmolites, suc ...
,
hunger In politics, humanitarian aid, and the social sciences, hunger is defined as a condition in which a person does not have the physical or financial capability to eat sufficient food to meet basic nutritional needs for a sustained period. In t ...
, and
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 ...
control.


Structure

The area postrema is a paired protuberance found at the inferoposterior limit of the
fourth ventricle The fourth ventricle is one of the four connected fluid-filled cavities within the human brain. These cavities, known collectively as the ventricular system, consist of the left and right lateral ventricles, the third ventricle, and the fourth ...
. Specialized
ependymal cells The ependyma is the thin neuroepithelial ( simple columnar ciliated epithelium) lining of the ventricular system of the brain and the central canal of the spinal cord. The ependyma is one of the four types of neuroglia in the central nervous sys ...
are found within the area postrema. These cells differ slightly from the majority of ependymal cells (ependymocytes), forming a unicellular epithelial lining of the ventricles and
central canal The central canal (also known as spinal foramen or ependymal canal) is the cerebrospinal fluid-filled space that runs through the spinal cord. The central canal lies below and is connected to the ventricular system of the brain, from which it r ...
. The area postrema is separated from the
vagal trigone The vagal trigone (ala cinerea) is a triangular eminence upon the rhomboid fossa produced by the underlying dorsal nucleus of vagus nerve. The vagal trigone is separated from the area postrema by a narrow strip of thickened ependyma The epend ...
by the
funiculus separans The vagal trigone (ala cinerea) is a triangular eminence upon the rhomboid fossa produced by the underlying dorsal nucleus of vagus nerve. The vagal trigone is separated from the area postrema by a narrow strip of thickened ependyma – the funic ...
, a thin semitransparent ridge. The vagal trigone overlies the
dorsal vagal nucleus The dorsal nucleus of vagus nerve (or posterior nucleus of vagus nerve or dorsal vagal nucleus or nucleus dorsalis nervi vagi or nucleus posterior nervi vagi) is a cranial nerve nucleus of the vagus nerve (CN X) situated in the medulla oblongata ...
and is situated on the caudal end of the
rhomboid fossa The rhomboid fossa is a rhombus-shaped depression that is the anterior part of the fourth ventricle. Its anterior wall, formed by the back of the pons and the medulla oblongata, constitutes the floor of the fourth ventricle. It is covered by a t ...
or 'floor' of the fourth ventricle. The area postrema is situated just before the
obex The obex () is the point in the human brain at which the fourth ventricle narrows to become the central canal of the spinal cord. Cerebrospinal fluid can flow from the fourth ventricle into the obex. In anatomical studies, the obex has been fo ...
, the inferior apex of the caudal ventricular floor. Both the funiculus separans and area postrema have a similar thick ependyma-containing tanycyte covering.
Ependyma The ependyma is the thin neuroepithelial ( simple columnar ciliated epithelium) lining of the ventricular system of the brain and the central canal of the spinal cord. The ependyma is one of the four types of neuroglia in the central nervous s ...
and
tanycytes Tanycytes are highly specialized ependymal cells found in the third ventricle of the brain, and on the floor of the fourth ventricle. Each tanycyte has a long basal process that extends deep into the hypothalamus. It is possible that their functio ...
can participate in the transport of
neurochemical A neurochemical is a small organic molecule or peptide that participates in neural activity. The science of neurochemistry studies the functions of neurochemicals. Prominent neurochemicals Neurotransmitters and neuromodulators *Glutamate is th ...
s into and out of 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 ...
from its cells or adjacent neurons, glia or vessels. Ependyma and tanycytes may also participate in chemoreception. The area postrema is considered a
circumventricular organ Circumventricular organs (CVOs) ( circum-: around ; ventricular: of ventricle) are structures in the brain characterized by their extensive and highly permeable capillaries, unlike those in the rest of the brain where there exists a blood–b ...
because of its proximity to the
ventricular system In neuroanatomy, the ventricular system is a set of four interconnected cavities known as cerebral ventricles in the brain. Within each ventricle is a region of choroid plexus which produces the circulating cerebrospinal fluid (CSF). The ventric ...
. In a morphological study, area postrema
capillaries A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima (the in ...
in the
ventral Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position prov ...
subregion of area postrema were shown to be relatively impermeable like those of the brain, whereas
medial Medial may refer to: Mathematics * Medial magma, a mathematical identity in algebra Geometry * Medial axis, in geometry the set of all points having more than one closest point on an object's boundary * Medial graph, another graph that repr ...
and
dorsal Dorsal (from Latin ''dorsum'' ‘back’) may refer to: * Dorsal (anatomy), an anatomical term of location referring to the back or upper side of an organism or parts of an organism * Dorsal, positioned on top of an aircraft's fuselage The fus ...
area postrema capillaries had microscopic characteristics of high permeability, a characteristic called
sinusoidal A sine wave, sinusoidal wave, or sinusoid (symbol: ∿) is a periodic wave whose waveform (shape) is the trigonometric sine function. In mechanics, as a linear motion over time, this is '' simple harmonic motion''; as rotation, it correspond ...
. Subregional capillary density of the area postrema was highest near the ventricular interface, and was nearly twice as dense as the capillary densities of the adjacent
solitary nucleus The solitary nucleus (SN) (nucleus of the solitary tract, nucleus solitarius, or nucleus tractus solitarii) is a series of neurons whose cell bodies form a roughly vertical column of grey matter in the medulla oblongata of the brainstem. Their a ...
(SN), and dorsal motor nucleus of the
vagus nerve The vagus nerve, also known as the tenth cranial nerve (CN X), plays a crucial role in the autonomic nervous system, which is responsible for regulating involuntary functions within the human body. This nerve carries both sensory and motor fibe ...
. A
tanycyte Tanycytes are highly specialized ependymal cells found in the third ventricle of the brain, and on the floor of the fourth ventricle. Each tanycyte has a long basal process that extends deep into the hypothalamus. It is possible that their functi ...
barrier partially compensates for high capillary permeability in the area postrema.
Physiological Physiology (; ) is the science, scientific study of function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a branches of science, subdiscipline of biology, physiology focuses on how organisms, organ syst ...
subregional studies of the area postrema indicated that its
blood volume Blood volume (volemia) is the volume of blood ( blood cells and plasma) in the circulatory system of any individual. Humans A typical adult has a blood volume of approximately 5 liters, with females and males having approximately the same blood p ...
is relatively large, and
blood flow Hemodynamics American and British English spelling differences#ae and oe, or haemodynamics are the Fluid dynamics, dynamics of blood flow. The circulatory system is controlled by homeostasis, homeostatic mechanisms of autoregulation, just as hydrau ...
and transit time for blood markers relatively slow, thereby amplifying the sensing capability for circulating compounds, such as hormones or transmitters.


Connections

The area postrema connects to the
solitary nucleus The solitary nucleus (SN) (nucleus of the solitary tract, nucleus solitarius, or nucleus tractus solitarii) is a series of neurons whose cell bodies form a roughly vertical column of grey matter in the medulla oblongata of the brainstem. Their a ...
, or nucleus tractus solitarii (NTS), and other autonomic control centers in 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 ...
. It is excited by visceral afferent impulses (sympathetic and vagal) arising from 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 ...
and other peripheral
trigger zone In neuroscience and neurology, a trigger zone is an area in the body, or of a cell, in which a specific type of stimulation triggers a specific type of response. The term was first used in this context around 1914 by Hugh T. Patrick, who was writin ...
s, and by humoral factors. The area postrema makes up part of the dorsal vagal complex, which is the critical termination site of vagal afferent nerve fibers, along with the
dorsal motor nucleus The dorsal nucleus of vagus nerve (or posterior nucleus of vagus nerve or dorsal vagal nucleus or nucleus dorsalis nervi vagi or nucleus posterior nervi vagi) is a cranial nerve nucleus of the vagus nerve (CN X) situated in the medulla oblongata ...
of the vagus and the NTS.
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 ...
is most likely induced via stimulation of the area postrema via its connection to the NTS, which may serve as the beginning of the pathway triggering vomiting in response to various emetic inputs. However, this structure plays no key role for nausea induced by the activation of vagal nerve fibers or by motion, and its function in radiation-induced vomiting remains unclear. Because the area postrema and a specialized region of NTS have permeable capillaries,
peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...
s and other hormonal signals in the blood have direct access to neurons of brain areas with vital roles in the autonomic control of the body. As a result, the area postrema is considered a site of integration for various physiological signals in the blood as they enter the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
.


Function


Chemoreception

The area postrema, one of the
circumventricular organs Circumventricular organs (CVOs) (wiktionary:circum-, circum-: around ; ventricular: of Ventricular system, ventricle) are structures in the brain characterized by their extensive and highly vascular permeability, permeable capillary, capillarie ...
, detects
toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...
s in the
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...
and acts as a vomit-inducing center. The area postrema is a critical homeostatic integration center for humoral and neural signals by means of its function as a
chemoreceptor trigger zone The chemoreceptor trigger zone (CTZ) is an area of the medulla oblongata that receives inputs from blood-borne drugs or hormones, and communicates with other structures in the vomiting center to initiate vomiting. The CTZ is located within the are ...
for
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 ...
in response to emetic drugs. It is a densely vascularized structure with subregional capillary specializations for high permeability for circulating blood signals, allowing it to detect various chemical messengers in the blood and
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 ...
. Capillary blood flow appears to be uniquely slow in the area postrema, prolonging the contact time for blood-borne hormones to interact with neuronal receptors involved in regulation of blood pressure, body fluids, and emetic responses.


Autonomic regulation

The fenestrated sinusoidal capillaries of the area postrema and a specialized region of NTS make this particular region of the
medulla Medulla (Latin for "marrow") or medullary may refer to: Science * Medulla oblongata, a part of the brain stem * Renal medulla, a part of the kidney * Adrenal medulla, a part of the adrenal gland * Medulla of ovary, a stroma in the center of the ...
critical in the autonomic control of various physiological systems, including the cardiovascular system and the systems controlling feeding and metabolism.
Angiotensin II Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the ...
causes a dose-dependent increase in
arterial blood pressure Blood pressure (BP) is the pressure of 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 "blood pressure" r ...
without producing considerable changes in the
heart rate Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...
, an effect mediated by the area postrema.


Clinical significance


Damage

Damage to the area postrema, caused primarily by lesioning or
ablation Ablation ( – removal) is the removal or destruction of something from an object by vaporization, chipping, erosion, erosive processes, or by other means. Examples of ablative materials are described below, including spacecraft material for as ...
, prevents the normal functions of the area postrema from taking place. This ablation is usually done surgically and for the purpose of discovering the exact effect of the area postrema on the rest of the body. Since the area postrema acts as an entry point to the brain for information from the
sensory neurons Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded receptor potentials. This process is called sensory transducti ...
of the stomach, intestines, liver, kidneys, heart, and other internal organs, a variety of physiological reflexes rely on the area postrema to transfer information. The area postrema acts to directly monitor the chemical status of the organism. Lesions of the area postrema are sometimes referred to as 'central vagotomy' because they eliminate the brain's ability to monitor the physiological status of the body through its vagus nerve. These lesions thus serve to prevent the detection of poisons and consequently prevent the body's natural defenses from kicking in. In one example, experiments done by Bernstein et al. on rats indicated that the area postrema lesions prevented the detection of
lithium chloride Lithium chloride is a chemical compound with the formula Li Cl. The salt is a typical ionic compound (with certain covalent characteristics), although the small size of the Li+ ion gives rise to properties not seen for other alkali metal chlorid ...
, which can become toxic at high concentrations. Since the rats could not detect the chemical, they were not able to employ a psychological procedure known as taste aversion conditioning, causing the rat to continuously ingest the lithium-paired saccharin solution. These findings indicate that rats with area postrema lesions do not acquire the normal conditioned taste aversions when lithium chloride is used as the unconditioned stimulus. In addition to simple taste aversions, rats with the area postrema lesions failed to perform other behavioral and physiological responses associated with the introduction of the toxin and present in the control group, such as lying down on their bellies, delayed stomach emptying, and hypothermia. Such experimentation emphasizes the significance of the area postrema not only in the identification of toxic substances in the body but also in the many physical responses to the toxin.


Effect of dopamine

The area postrema also has a significant role in the discussion of
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
. Drugs that treat Parkinson's disease using
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 ...
have a strong effect on the area postrema. These drugs stimulate dopamine transmission and attempt to normalize motor functions affected by Parkinson's. This works because nerve cells, in particular, in the
basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...
, which has a crucial role in the regulation of movement and is the primary site for the pathology of Parkinson's, use dopamine as their neurotransmitter and are activated by medications that increase the concentrations of the dopamine or work to stimulate the dopamine receptors. Dopamine also manages to stimulate the area postrema, since this part of the brain contains a high density of dopamine receptors. The area postrema is very sensitive to changes in blood toxicity and senses the presence of poisonous or dangerous substances in the blood. As a defense mechanism, the area postrema induces vomiting to prevent further intoxication. The high density of dopamine receptors in the area postrema makes it very sensitive to the dopamine-enhancing drugs. Stimulation of the dopamine receptors in the area postrema activates these vomiting centers of the brain; this is why nausea is one of the most common side-effects of antiparkinsonian drugs.


History

The area postrema was first named and located in the gross anatomy of the brain by Magnus
Gustaf Retzius Prof Magnus Gustaf (or Gustav) Retzius FRSFor HFRSE MSA (17 October 1842 – 21 July 1919) was a Swedish physician and anatomist who dedicated a large part of his life to researching the histology of the sense organs and nervous system. Lif ...
, a Swedish anatomist, anthropologist and professor of
histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...
. In 1896, he published a two-volume monograph on the gross anatomy of the human brain in which the area postrema was mentioned. In 1975, evidence of neurons in the area postrema of several mammal species was published. Scientists became increasingly interested in the research of vomiting in the 1950s, perhaps in part due to society's heightened awareness of
radiation sickness Acute radiation syndrome (ARS), also known as radiation sickness or radiation poisoning, is a collection of health effects that are caused by being exposed to high amounts of ionizing radiation in a short period of time. Symptoms can start wit ...
, a condition in which many patients having vomited after radiation exposure died. Studies showed the existence of two areas in the brain related to emesis: one, a chemosensor for vomiting with no coordinating function, located in the fourth ventricle and two, a coordinator of vomiting with no chemosensory function, located in the lateral reticular formation of the medulla oblongata. In 1953, Borison and Wang determined that the chemosensor area acted as a vomiting trigger zone in the brain stem, which they named the chemoreceptor trigger zone (CTZ) for emesis. Using cats and dogs as model organisms, they found that the removal of this trigger zone from the brain allowed for the prevention of emesis in the animals directly following injection of certain chemicals into the blood, demonstrating the existence of a relationship between the trigger zone and the act of vomiting. The CTZ was anatomically located in the area postrema of the medulla oblongata. The area postrema had been anatomically identified and named nearly 60 years earlier, but its function had remained unknown until its role in emesis was later confirmed.


Current research

Research has continued today around the world on the functions of the area postrema. Beyond its role in emesis, as studied intensely by the researchers of the mid-1900s, the activity of the area postrema has been closely linked to other autonomic functions such as regulation of food intake, body fluid homeostasis, and
cardiovascular In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart a ...
regulation through behavioral studies and
electrophysiological Electrophysiology (from ee the Electron#Etymology, etymology of "electron" ; and ) is the branch of physiology that studies the electrical properties of biological cell (biology), cells and tissues. It involves measurements of voltage change ...
studies. In 2007 in Japan, research was performed on the mechanism of excitability of area postrema neurons by extracellular ATP.
Voltage clamp The voltage clamp is an experimental method used by electrophysiologists to measure the ion currents through the membranes of excitable cells, such as neurons, while holding the membrane voltage at a set level. A basic voltage clamp will iter ...
whole-cell recording techniques were used on rat brain slices. The results showed that most responses to ATP are excitatory and that they are mediated by particular P2 purinoceptors found in the area postrema. The role of the area postrema in flavor-conditioned aversion and preference was studied in 2001 by researchers at the
Brooklyn College Brooklyn College is a public university in Brooklyn in New York City, United States. It is part of the City University of New York system and enrolls nearly 14,000 students on a campus in the Midwood and Flatbush sections of Brooklyn as of fall ...
at the
City University of New York The City University of New York (CUNY, pronounced , ) is the Public university, public university system of Education in New York City, New York City. It is the largest urban university system in the United States, comprising 25 campuses: eleven ...
. The experiment tested the effect of area postrema lesions in rats on their ability to learn flavor-conditioned aversion to flavors paired with toxic drug treatments, which indeed showed that lesions of the area postrema leads to impaired flavor aversion learning. A 2009 study followed the development of the area postrema, using a macaque monkey model in an attempt to identify and characterize
neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron ...
in this region as well as to resolve outstanding incongruities across research. These scientists found, in culmination, that previous studies suggest
noradrenalin Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone, neurotransmitter and neuromodulator. The name "noradrenaline" (from L ...
and/or dopamine cause CA fluorescence in the area postrema macaque-CA, meaning catecholaminergic or derived from an amine and functioning as a
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 ...
or hormone or both. The study, however, found evidence of neurotransmitter secretion instead of release in vesicles. Also, their findings concluded
GABA GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...
is a major neurotransmitter in the area postrema, not
glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...
. Ongoing research continues to unravel discrepancies among various rat, cat, and now macaque monkey models of research.


Potential treatments

A 2002 study in Japan tested a drug that may be of use in curbing the emetic response to drugs that increase dopamine concentrations. The study investigated morphine-induced emesis in ferrets, explaining that morphine exposure triggered dopamine release in the medulla oblongata and in the area postrema by activating opiate receptors, which in turn caused vomiting by the ferrets. Yet a pre-treatment with 6-hydroxydopamine, a dopaminergic
neurotoxin Neurotoxins are toxins that are destructive to nervous tissue, nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insult (medical), insultsSpencer 2000 that can adversely affect function ...
, significantly reduced the number of emetic episodes in the ferrets following morphine exposure. This neurotoxin reduced levels of dopamine, noradrenaline, and homovanillic acid, a metabolite of dopamine, and is known to destroy noradrenergic and dopaminergic neurons. Here, 6-hydroxydopamine was injected directly into the medulla oblongata but not in other parts of the brain. This study shows how the dopaminergic pathway in the medulla oblongata may be manipulated in order to reduce the nauseating side-effects associated with so many dopamine-increasing drugs.


Continuing pathological studies

The area postrema is also indicated in an
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 ...
treatment against type 1 and type 2 diabetes. A particular mechanism, employed by the drug
pramlintide Pramlintide (trade name Symlin) is an injectable amylin analogue drug for diabetes (both type 1 and 2), developed by Amylin Pharmaceuticals (now a wholly owned subsidiary of AstraZeneca). Pramlintide is sold as an acetate salt. Pharmacology Pram ...
, acts mainly on the area postrema and results in decreased
glucagon Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises the concentration of glucose and fatty acids in the bloodstream and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medic ...
secretion, which in turn slows down gastric emptying and the satiety effect. This targeting of the area postrema allows an improvement of glycaemic control without causing weight gain. Since the drug acts on the area postrema, the doses must be titrated slowly to avoid inducing nausea in the patient. There are also studies still currently underway to determine the effect of ablation of the area postrema on
hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...
and cardiovascular function. For example, studies in rats and rabbits indicate that
angiotensin II Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the ...
- dependent hypertension is abolished by lesioning of the area postrema. The mechanism for this physiological reaction is still not fully understood, but the area postrema's ability to regulate cardiovascular function presents a very interesting direction for neuroendocrinology.


References

{{DEFAULTSORT:Area Postrema Medulla oblongata Vomiting