Dopamine- a neurotransmitter of the central nervous system, as well as a mediator of local nervous (paracrine) regulation in a number of peripheral organs (including the mucous membrane of the gastrointestinal tract, kidneys). It is also a hormone produced by the adrenal medulla and other tissues (for example, kidneys), but this hormone almost does not penetrate into the subcortex of the brain from the blood. Based on its chemical structure, dopamine is classified as a catecholamine. Dopamine is a biochemical precursor of norepinephrine and adrenaline during their synthesis.

Norepinephrine Adrenaline

Story

Dopamine was first synthesized in 1910, but for many years it was considered only a precursor to adrenaline and norepinephrine. It wasn't until 1958 that Swedish scientist Arvid Carlsson discovered that dopamine is the most important neurotransmitter in the brain. More than 40 years later, in 2000, he was awarded the Nobel Prize in Physiology or Medicine for this discovery.

A laboratory rat in a special box presses a lever. Stimulators are attached to the animal's head.

In a seminal 1954 study, Canadian scientists James Olds and his colleague Peter Milner found that if electrodes were implanted in specific areas of the brain, especially the mid-forebrain ganglion, rats could be trained to press a lever in a cage that triggered low-voltage electrical stimulation. Once the rats learned to stimulate this area, they pressed the lever up to a thousand times per hour. This gave reason to assume that the pleasure center is stimulated. One of the main pathways for the transmission of nerve impulses in this part of the brain is dopamine, so researchers have put forward the theory that the main chemical associated with pleasure is dopamine. This assumption was later confirmed by radionuclide tomography scanners and the discovery of antipsychotics (medicines that suppress the productive symptoms of schizophrenia).

However, in 1997, dopamine was shown to play a more subtle role. In Schultz's experiment, a conditioned reflex was created in a monkey according to the classical Pavlovian scheme: after a light signal, juice was injected into the monkey's mouth.

The results suggested that dopamine is involved in the formation and consolidation of conditioned reflexes during positive reinforcement and in extinguishing them if the reinforcement stops. In other words, if our expectation of reward is met, the brain tells us this by releasing dopamine. If the reward does not follow, a decrease in dopamine levels signals that the model has diverged from reality. Further work showed that the activity of dopamine neurons is well described by the well-known model of automata learning: actions that quickly lead to receiving a reward are assigned greater value. This is how learning occurs through trial and error.

Neurotransmitter

Dopamine is one of the intrinsic reinforcement chemicals (IRFs) and serves as an important part of the brain’s “reward system” because it produces feelings of pleasure (or satisfaction), which influences motivation and learning processes. Dopamine is naturally produced in large quantities during what a person perceives as a positive experience - for example, eating tasty food, pleasant bodily sensations, and drugs. Neurobiological experiments have shown that even memories of reward can increase dopamine levels, so this neurotransmitter is used by the brain for assessments and motivation, reinforcing actions important for survival and continuation of the species.

Dopamine plays an important role in ensuring cognitive activity. Activation of dopaminergic transmission is necessary during the processes of switching a person’s attention from one stage of cognitive activity to another. Thus, insufficiency of dopaminergic transmission leads to increased inertia of the patient, which is clinically manifested by slowness of cognitive processes (bradyphrenia) and perseverations. These disorders are the most typical cognitive symptoms of diseases with dopaminergic deficiency - for example, Parkinson's disease.

Like most neurotransmitters, dopamine has synthetic analogues, as well as stimulators of its release in the brain. In particular, many drugs increase the production and release of dopamine in the brain by 5-10 times, which allows people who use them to experience feelings of pleasure in an artificial way. Thus, amphetamine directly stimulates the release of dopamine, affecting its transport mechanism.

Other drugs, such as cocaine and some other psychostimulants, block the natural mechanisms of dopamine reuptake, increasing its concentration in the synaptic space.

Morphine and cotins mimic the effect of natural neurotransmitters, and alcohol blocks the effect of dopamine antagonists. If the patient continues to overstimulate his reward system, the brain gradually adapts to the artificially increased dopamine levels, producing less of the hormone and reducing the number of receptors in the reward system, one of the factors that encourages the addict to increase the dose to get the same effect. Further development of chemical tolerance can gradually lead to metabolic disorders in the brain, and in the long term, potentially cause serious damage to brain health

To treat Parkinson's disease, dopamine receptor agonists (that is, dopamine analogues: pramipexole, bromocriptine, pergolide, etc.) are often used: today this is the largest group of antiparkinsonian drugs. Some antidepressants also have dopaminergic activity.

There are also medications that block dopaminergic transmission, for example, antipsychotics such as caminazine, haloperidol, risperidone, clozapine, etc. Reserpine blocks the pumping of dopamine into presynaptic vesicles.

For mental illnesses such as schizophrenia and obsessive-compulsive disorder ((from Lat. obsessio- “siege”, “envelopment”, lat. obsessio- “obsession with an idea” and lat. compello- “I force”, lat. compulsio- “coercion”) ( OCD, obsessive-compulsive neurosis) - mental disorder. It can be chronic, progressive or episodic in nature.), there is increased dopaminergic activity in some brain structures, in particular in the limbic pathway (in schizophrenia, there is also decreased dopamine activity in the mesocortical dopamine pathway and prefrontal cortex), aparkinsonism is associated with a decreased content of dopamine in the nigrostriatal pathway. The process of normal aging is also associated with a decrease in dopamine levels in the subcortical formations and anterior parts of the brain.

Hormone

Dopamine has a number of physiological properties characteristic of adrenergic substances.

Dopamine causes an increase in peripheral vascular resistance. It increases systolic blood pressure as a result of stimulation of α-adrenergic receptors. Dopamine also increases the force of heart contractions as a result of stimulation of β-adrenergic receptors. The heart rate increases, but not as much as under the influence of adrenaline.

As a result of specific binding to dopamine receptors in the kidneys, dopamine reduces the resistance of the renal vessels, increases blood flow and renal filtration, and increases natriuresis. Dilation of the mesenteric vessels also occurs. This effect on the renal and mesenteric vessels distinguishes dopamine from other catecholamines (norepinephrine, adrenaline, etc.). However, in high concentrations, dopamine can cause vasoconstriction in the kidneys.

Dopamine also inhibits the synthesis of aldosterone in the adrenal cortex, reduces the secretion of renin by the kidneys, and increases the secretion of prostaglandins by the kidney tissue.

Dopamine inhibits gastric and intestinal peristalsis, causes relaxation of the lower esophageal sphincter and increases gastroesophageal and duodeno-gastric reflux. VCNS dopamine stimulates the chemoreceptors of the trigger zone and the vomiting center and thereby takes part in the act of vomiting.

Dopamine penetrates little through the blood-brain barrier, and increased levels of dopamine in the blood plasma have little effect on the functions of the central nervous system, with the exception of the effect on areas outside the blood-brain barrier, such as the trigger zone.

An increase in the level of dopamine in the blood plasma occurs during shock, injury, burns, blood loss, stressful conditions, during various pain syndromes, anxiety, fear, stress. Dopamine plays a role in the body’s adaptation to stressful situations, injuries, blood loss, etc.

Also, the level of dopamine in the blood increases with deterioration of blood supply to the kidneys or with an increased content of sodium ions, as well as angiotensin or aldosterone in the blood plasma. Apparently, this occurs due to an increase in the synthesis of dopamine from DOPA in kidney tissue during ischemia or under the influence of angiotensin and aldosterone. It is likely that this physiological mechanism serves to correct renal ischemia and to counteract hyperaldosteronemia and hypernatremia.

Biosynthesis

The precursor to dopamine is L-tyrosine (it is synthesized from phenylalanine), which is hydroxylated by the enzyme tyrosine hydroxylase to form L-DOPA, which in turn is decarboxylated by the enzyme L-DOPA decarboxylase and converted to dopamine. This process occurs in the cytoplasm of the neuron.

In sympathetic nerve endings, synthesis proceeds to the stage of norepinephrine, which functions as a neurotransmitter in sympathetic synapses. Cells similar to the chromaffin cells of the adrenal medulla are found in other tissues. Clusters of such cells are found in the heart, liver, kidneys, gonads, etc. Islands of such tissue function similarly to the adrenal medulla and are subject to similar pathological changes.

Inactivated by methylation and by oxidation by the enzyme monoamine oxidase (MAO). Dopaminergic neurons are located in the subcortical nuclei of the midbrain (substantia nigra, striatum) and in the hypothalamus. They send impulses to the pituitary gland and limbic system. There the regulation of muscle tone, emotional state, and behavior occurs.

Dopaminergic system

Of all the neurons in the central nervous system, about seven thousand produce dopamine. There are several known dopamine nuclei located in the brain. This is the arcuate nucleus (lat. nucleus arcuatus), giving its processes to the median eminence of the hypothalamus. Dopamine neurons in the substantia nigra send axons to the striatum (caudate and lenticular nuclei). Neurons located in the ventral tegmental area give projections to the climbic structures of the cortex.

The main dopamine pathways are:

mesocortical pathway (motivational processes and emotional reactions)

mesolimbic pathway (producing feelings of pleasure, reward and desire)

nigrostriatal pathway (motor activity, extrapyramidal system)

Neuron cell bodies nigrostriatal, mesocortical And mesolimbic tracts form a complex of neurons of the substantia nigra and the ventral tegmental field. The axons of these neurons first go as part of one large tract (medial bundle of the forebrain), and then diverge into various brain structures.

In the extrapyramidal system, dopamine plays the role of a stimulating neurotransmitter, helping to increase motor activity, reduce motor retardation and stiffness, and reduce muscle hypertonicity. Physiological antagonists of dopamine in the extrapyramidal system are acetylcholine GABA.

Receptors

Postsynaptic dopamine receptors belong to the GPCR family. There are at least five different dopamine receptor subtypes - D 1-5. The D 1 and D 5 receptors have quite significant homology and are associated with the GS protein, which stimulates adenylate cyclase, as a result of which they are usually considered together as D 1 -like receptors. The remaining receptors of the subfamily are similar to D2 and are associated with the Gi protein, which inhibits adenylate cyclase, as a result of which they are combined under the general name D-2-like receptors. Thus, dopamine receptors play the role of modulators of long-term potentiation.

D 2 and D 4 receptors take part in “internal reinforcement”.

In high concentrations, dopamine also stimulates α- and β-adrenergic receptors. The effect on adrenergic receptors is associated not so much with direct stimulation of adrenergic receptors, but with the ability of dopamine to release norepinephrine from granular presynaptic depots, that is, to have an indirect adrenomimetic effect.

"Cycle" of dopamine

The dopamine synthesized by the neuron accumulates in dopamine vesicles (the so-called “synaptic vesicle”). This process is proton-coupled transport. H + ions are pumped into the vesicle using a proton-dependent ATPase. When protons are released along the gradient, dopamine molecules enter the vesicle.

Next, dopamine is released into the synaptic cleft. Part of it is involved in the transmission of nerve impulses, acting on cellular D-receptors of the postsynaptic membrane, and part is returned to the presynaptic neuron using reuptake. Autoregulation of dopamine release is provided by D 2 and D 3 receptors on the membrane of the presynaptic neuron. Reuptake is carried out by the dopamine transporter. The mediator that returns to the cell is cleaved by monoamine oxidase (MAO) and, further, by aldehyde dehydrogenase and catechol-O-methyl-transferase of dohomovanillic acid.

Pathologies

The role of disturbances in dopamine transmission in parkinsonism, MDP, and schizophrenia has been confirmed. In patients with schizophrenia, the level of homovanillic acid (HVA), which is a product of the transformation and inactivation of dopamine, is increased compared to the norm.

A decrease in HVA levels may indicate the effectiveness of treatment with antipsychotics. The action of dopamine is associated with the appearance of such productive symptoms of schizophrenia as delusions, hallucinations, mania, and motor agitation. The antidopamine effect of aminazine and other neuroleptics leads to complications such as tremor, muscle stiffness, restlessness, and akathisia.

The most well-known pathologies associated with dopamine are schizophrenia and parkinsonism, as well as obsessive-compulsive disorder.

Various independent studies have shown that many individuals with schizophrenia have increased dopaminergic activity in some brain structures and decreased dopaminergic activity in the mesocortical pathway and prefrontal cortex. Antipsychotics (neuroleptics) are used to treat schizophrenia, which block dopamine receptors (mainly D2-type) and vary in the degree of affinity for other significant neurotransmitter receptors. Typical antipsychotics mainly suppress D2 receptors, and new atypical antipsychotics and some of the typical ones act simultaneously on a number of neurotransmitter receptors: dopamine, serotonin, histamine, acetylcholine and others.

It is assumed that a decrease in dopamine levels in the mesocortical pathway is associated with negative symptoms of schizophrenia (flattening of affect, apathy, poor speech, anhedonia, withdrawal from society), as well as with cognitive disorders (deficits of attention, working memory, executive functions).

The antipsychotic effect of neuroleptics, that is, their ability to reduce productive disorders - delusions, hallucinations, psychomotor agitation - is associated with inhibition of dopaminergic transmission in the mesolimbic pathway. Neuroleptics also inhibit dopaminergic transmission in the mesocortical pathway, which with long-term therapy often leads to increased negative disorders.

Parkinsonism is associated with decreased levels of dopamine in the nigrostriatal pathway. Observed with the destruction of the substantia nigra, pathology of D-1-like receptors. The development of extrapyramidal side effects when taking antipsychotics: drug-induced parkinsonism, dystonia, akathisia, tardive dyskinesia, etc. is also associated with the inhibition of dopaminergic transmission in the nigrostriatal system.

Disorders of the dopaminergic system are associated with disorders such as anhedonia, depression, dementia, pathological aggressiveness, fixation of pathological drives, persistent lactorrhea-amenorrhea syndrome, impotence, acromegaly, restless legs syndrome and periodic limb movements.

Dopamine theory of schizophrenia

The dopamine (aka catecholamine) hypothesis places special emphasis on dopaminergic activity in the mesolimbic pathway of the brain.

The so-called “dopamine theory of schizophrenia” or “dopamine hypothesis” was put forward; According to one of its versions, patients with schizophrenia learn to gain pleasure by concentrating on thoughts that cause the release of dopamine and thereby overstrain their “reward system,” damage to which causes symptoms of the disease. There are several different schools of thought among proponents of the “dopamine hypothesis,” but in general, it links the productive symptoms of schizophrenia to disturbances in the brain’s dopamine systems. The “dopamine theory” was very popular, but its influence has weakened in our time; now many psychiatrists and schizophrenia researchers do not support this theory, considering it too simplified and unable to provide a complete explanation of schizophrenia. This revision was partly facilitated by the emergence of new (“atypical”) antipsychotics, which, while similar in effectiveness to older drugs, have a different spectrum of effects on neurotransmitter receptors.

The primary defect in dopaminergic transmission in schizophrenia could not be established, since researchers obtained different results when functionally assessing the dopaminergic system. The results of determining the level of dopamine and its metabolites in the blood, urine and cerebrospinal fluid were inconclusive due to the large volume of these biological media, which neutralized possible changes associated with limited dysfunction of the dopaminergic system.

Numerous attempts to confirm this hypothesis were primarily aimed at determining the main product of dopamine metabolism - homovanillic acid - in the cerebrospinal fluid of patients. However, the vast majority of researchers were unable to detect significant, much less specific changes in the content of homovanillic acid in the cerebrospinal fluid of patients.

Considering schizophrenia as a disease associated with dysregulation of the dopamine system required measuring the activity of the enzyme dopamine β-hydroxylase, which converts dopamine into norepinephrine. Reduced activity of this key enzyme in the brain tissues of patients with schizophrenia may cause the accumulation of dopamine and a decrease in the level of norepinephrine in the tissues. Such data could provide significant support for the dopamine hypothesis of schizophrenia. This assumption was tested in studies of the level of dopamine β-hydroxylase in the cerebrospinal fluid of patients and in the study of autopsy material (brain tissue). The content and activity of dopamine-(3-hydroxylase) did not differ significantly compared to control studies.

The results of studying the activity of these enzymes and corresponding substrates in the peripheral blood of patients do not bring us closer to understanding the role of dopaminergic systems of the brain in the pathogenesis of psychoses. The fact is that fluctuations in the activity and level of specific enzymes of the dopamine system, as well as dopamine itself, in the periphery do not reflect the state of these same systems at the brain level. Moreover, changes in the level of dopamine activity in the brain receive physiological expression only when they occur in strictly defined brain structures (striatum area, limbic system). In this regard, the development of the dopamine hypothesis has methodological limitations and cannot follow the path of measuring the content of dopamine and related compounds in the peripheral blood and urine of mentally ill patients.

A few studies have attempted to study the state of the dopamine system using postmortem brain tissue from patients. Hypersensitivity of dopamine receptors, which are affinity for ZN-apomorphine, was established in the limbic region and striatum of the brain of patients with schizophrenia. However, serious evidence is needed that this hypersensitivity (increase in the number of receptors) is not a consequence of drug induction, i.e., not caused by chronic administration of psychotropic compounds to the examined patients.

Some researchers have tried to confirm the dopamine hypothesis of schizophrenia by measuring the levels of the hormone prolactin in the blood plasma of patients before and during treatment with antipsychotics. The release of prolactin from the pituitary gland is regulated by the dopamine system of the brain, the hyperactivity of which should lead to an increase in its content in the blood. However, no noticeable changes in prolactin levels were observed in patients not treated with psychotropic drugs, and examination of treated patients gave inconclusive and contradictory results.

Thus, a number of pharmacological and biochemical data indicate a connection between the development of mental disorders and changes in the function of the dopamine system of the brain at the synaptic and receptor levels. However, indirect methods of testing the dopamine hypothesis of schizophrenia have not yet yielded positive results. However, all these approaches may not be sufficiently adequate to study the mechanisms of disruption of the dopamine system at the brain level. For example, if psychosis-causing changes in dopamine activity are localized only in such isolated brain structures as the limbic region, then all modern methods for determining this activity in biological fluids (even in the cerebrospinal fluid) will be unsuitable for proving this fact. The acceptability of the dopamine hypothesis for explaining the nature of schizophrenia will be finally established with the advent of more sensitive methods and adequate approaches to the study of chemical disorders at the level of the human brain.

Dopaminergic concept of parkinsonism

Already in the process of studying the morphological picture of parkinsonism, one feature was noticed that is characteristic of this disease and consists in a peculiar pathomorphological tropism: the structures containing pigment are primarily affected. This mystery has now been largely solved. It has become known that the pigment neuromelanin, contained in some brain structures, is formed from catecholamines (from dopa and dopamine) by oxidative polymerization. The brain in Parkinsonism gradually loses melanin reserves, but the significance of this fact remained unclear for a long time. The pathways for melanin synthesis in the central nervous system differ from those in other tissues of the body, since normal pigmentation of the substantia nigra occurs even in albinos. The importance of pigment metabolism in the pathogenesis of the disease is apparently also indicated by the fact that parkinsonism is significantly less common among representatives of the Negroid race. Rare observations in which malignancy of melanoma was noted in patients with parkinsonism during treatment with 1-dopa indicate the same thing.

The significant progress that has been made in recent years in the treatment of patients with parkinsonism is largely due to the achievements of functional neurochemistry, thanks to which the dopaminergic concept of parkinsonism was substantiated. Although dopamine was first synthesized back in 1909, its presence in the brains of healthy people was discovered only in 1958. The neurochemical aspects of parkinsonism began to be intensively developed in 1960, when it was discovered that in the brains of patients with parkinsonism there is a deficiency of dopamine, resulting from degenerative process in neurons of the substantia nigra. Since then, the efforts of many researchers have been aimed at finding methods and means that would increase the content of dopamine in the central nervous system of these patients. Dopamine itself cannot be used for this purpose, since it does not penetrate the blood-brain barrier well. In 1960, it was proposed to use not dopamine for medicinal purposes, but its predecessor, dioxyphenylalanine (dopa), which, penetrating the central nervous system, undergoes decarboxylation and turns into dopamine, replenishing its deficiency in brain tissue. A synthetic levorotatory isomer of dioxyphenylalanine (1-dopa) was used, which proved to be more effective than the dextrorotatory isomer. Already in 1961, the first results of treating patients with parkinsonism using the drug 1-dopa were published. These works quickly gained worldwide fame and served as a stimulus for wider study of the monoaminergic biochemical systems of the human and animal brain, as well as the neurochemical aspects of parkinsonism.

Dopamine

Active substance

›› Dopamine*

Latin name

Pharmacological groups: Cardiac glycosides and non-glycoside cardiotonic drugs
›› Dopaminomimetics
›› Hypertensive drugs

Composition and release form

Substance for the preparation of dosage forms; in jars of 800 g.

pharmachologic effect

pharmachologic effect- cardiotonic, vasoconstrictive.

Best before date

Storage conditions

List B.: In a place protected from light.

* * *

DOPAMINE "(Dophaminum, Dofaminum). 2-(3,4-Dioxyphenyl)-ethylamine, or oxytyramine. Synonyms: Dopamine, Dopmin, Aprical, Cardiosteril, Dopamex, Dopamin, Dophan, Dopmin, Dynatra, Hydroxytyramin, Intropin, Revivan. For used as a drug, dopamine is obtained synthetically. The chemical structure of dopamine is a catecholamine and has a number of pharmacological properties characteristic of adrenergic substances. It has a specific effect on dopamine receptors, for which it is an endogenous ligand, but in large doses it also stimulates a and b-adrenergic receptors. The effect on adrenergic receptors is associated with the ability of dopamine to release norepinephrine from granular (presynaptic) depots, i.e., have an indirect adrenomimetic effect. Under the influence of dopamine, there is an increase in peripheral vascular resistance (less strong than under the influence of norepinephrine) and an increase in systolic arterial blood pressure. pressure (the result of stimulation of β-adrenergic receptors), increased heart contractions (the result of stimulation of β-adrenergic receptors), and increased cardiac output. The heart rate changes relatively little. Myocardial oxygen demand increases, but increased coronary blood flow results in increased oxygen delivery. As a result of specific binding to dopamine receptors in the kidneys, dopamine reduces the resistance of the renal vessels, increases blood flow and renal filtration. Along with this, natriuresis increases, and dilation of the mesenteric vessels also occurs. This effect on the renal and mesenteric vessels distinguishes dopamine from other catecholamines (norepinephrine, adrenaline, etc.). In large doses, however (when administered to humans in doses exceeding 15 mcg/kg per minute), dopamine can cause renal vasoconstriction. Dopamine also inhibits aldosterone synthesis. The pharmacological effects of dopamine occur when administered intravenously; when introduced into the stomach, it is poorly absorbed. Due to the fact that it degrades quickly, the main method of its use is a slow drip infusion. Dopamine does not penetrate the blood-brain barrier and, when administered into a vein, does not affect the central nervous system (see Drugs for the treatment of parkinsonism). Indications for the use of dopamine are shock conditions of various etiologies: cardiogenic, traumatic, endotoxic, postoperative, hypovolemic shock, etc. Due to its lesser effect on peripheral vascular resistance, increased renal blood flow and blood flow in other internal organs, less chronotropic effect and other features of dopamine considered in these cases to be more indicated than norepinephrine and other catecholamines. Dopamine is also used to improve hemodynamics in acute cardiac and vascular failure that develops in various pathological conditions. Dopamine is administered intravenously; 25 or 200 mg of the drug are diluted, respectively, in 125 or 400 ml of 5% glucose solution or isotonic sodium chloride solution (the dopamine content in 1 ml is 200 or 500 mcg, respectively). The initial rate of administration is 1 - 5 mcg/kg per minute (2 - 11 drops of a 0.05% solution). If necessary, the rate of administration is increased to 10 - 25 mcg/kg per minute (average 18 mcg/kg per minute). The infusion is carried out continuously for 2 - 3 hours to 1 - 4 days. The daily dose reaches 4OO - 8OO mg. The effect of the drug occurs quickly and ceases 5 to 10 minutes after the end of administration. The optimal dose must be selected in each individual case under constant monitoring of hemodynamics and ECG. It must be taken into account that exceeding the optimal doses of dopamine can lead to a significant increase in cardiac work, which can increase local and general ischemia and negatively affect the functional state of the ischemic myocardium. Large doses of dopamine can cause tachycardia and arrhythmias, renal vasoconstriction. A decrease in urine output without hypotension indicates the need for dose reduction. With the development of arrhythmias, it is advisable to use antiarrhythmic drugs (lidocaine, etc.). In case of hypovolemic shock, the use of dopamine should be combined with the administration of plasma or plasma replacement drugs (or blood). Release form: 0.5% or 4% solution in ampoules of 5 ml (25 or 200 mg of dopamine). Storage: List B. In a place protected from light.

• - Dopamine Active ingredient ›› Dopamine * Latin name Dofaminum Pharmacological groups: Cardiac glycosides and non-glycoside cardiotonic drugs ›› Dopaminomimetics ›› Hypertensive drugs Composition and...

  Medicines

• - a chemical substance usually found in the striatum region of the human brain; its deficiency leads to the development of PARKINSON'S DISEASE...

  Scientific and technical encyclopedic dictionary

• - dopamine - .Neurohormone from the group of catecholamines, a neurotransmitter of the nervous system...

  Molecular biology and genetics. Dictionary

• - nerve mediator systems from the catecholamine group, neurohormone. Biochem. precursor of norepinephrine and adrenaline. Produced by nerve endings, as well as chromaffin cells...

  Natural science. encyclopedic Dictionary

• - 3,4-dioxyphenylethylamine, oxytyramine, C6H32CH2CH2, an intermediate product of catecholamine biosynthesis, resulting from the decarboxylation of dioxyphenylalanine...

  Great Soviet Encyclopedia

• - dopham "...

  Russian spelling dictionary

• - dopamine is an intermediate product of catecholamine biosynthesis; along with adrenaline and norepinephrine, it is secreted by the adrenal medulla...

  Dictionary of foreign words of the Russian language

• - noun, number of synonyms: 5 hormone dihydroxyphenylalanine catecholamine monamine neurohormone...

  Synonym dictionary

"DOPAMINE" in books

How good, oh dear dopamine!

by Helen Fisher

How good, oh dear dopamine!

From the book Why We Love [The Nature and Chemistry of Romantic Love] by Helen Fisher

How good, oh dear dopamine! Let's take dopamine. Increasing the level of dopamine in the brain leads to concentration, (2) increased motivation, makes a person focus on achieving a goal. (3) These are the three most important characteristics of romantic passion. Lovers

Dopamine

From the book Great Soviet Encyclopedia (DO) by the author TSB

LECTURE 13. Dopamine and dopaminergic drugs

author

LECTURE 13. Dopamine and dopaminergic drugs 1. Dopamine Dopamine is a biogenic amine formed from l-tyrosine and is a precursor of norepinephrine and adrenaline and a mediator that interacts with α- and β-adrenergic receptors, as well as with specific receptors,

1. Dopamine

From the book Pharmacology: lecture notes author Malevannaya Valeria Nikolaevna

1. Dopamine Dopamine is a biogenic amine formed from l-tyrosine and is a precursor of norepinephrine and adrenaline and a mediator that interacts with α- and β-adrenergic receptors, as well as with specific receptors called dopamine and located

39. Dopamine

From the book Pharmacology author Malevannaya Valeria Nikolaevna

39. Dopamine Dopamine is a biogenic amine formed from l-tyrosine and is a precursor of norepinephrine and adrenaline and a mediator that interacts with a- and b-adrenergic receptors, as well as with specific receptors called dopamine and

Dopamine

From the book Analyzes. Complete guide author Ingerleib Mikhail Borisovich

Dopamine is the precursor of adrenaline. Changes - see "Adrenaline". Peculiarities of the test: usually tested in urine, urine is collected within 24 hours. Norm: in blood serum - less than 30-40 ng / l; in urine: children under 1 year – less than 180 mcg/day, children 1–2 years – less

Dopmin Synonyms. Dopamine, Dopamine

From the book Modern Medicines for Children author Pariyskaya Tamara Vladimirovna

Dopmin Synonyms. Dopamine, Dopamine Group of drugs. Medicines used for circulatory failure. Composition and release form. Solution for infusion in ampoules of 5 ml (1 ml of solution contains 40 mg of dopamine hydrochloride) in

Dopamine

From the book How not to turn into Baba Yaga by Nonna Doctor

Dopamine When a person receives some positive experience (and satisfaction of needs is certainly a positive experience) - eats or procreates (has sex), successfully studies or works, swims in the sea or dances - is produced in large quantities in his brain

From the book Nutrition for the Brain. An effective step-by-step technique for enhancing brain efficiency and strengthening memory by Barnard Neal

So what does Dopamine have to do with it? Why do people take drugs if they pose such a deadly danger - they can get you in trouble with the police, ruin your career, and even die prematurely? It's all about dopamine. In the depths of your brain, in

Chapter 7 Why Wall Street Crash But Warren Buffett Is Still Thriving Introverts and Extroverts Think (and Respond to Dopamine) Differently

From the book Introverts [How to use your personality traits] by Kane Susan

Chapter 7 Why Wall Street Crash but Warren Buffett Still Thrives Introverts and Extroverts Think Differently (and Respond to Dopamine) Tocqueville understood that in a world of constant action and decision-making that was shaped by

Making lists is rewarding in itself because it activates the dopamine system. Dopamine (dopamine) is a neurotransmitter that is responsible for the anticipation of a result and is necessary for memorization and learning. Until 2003, they thought that it was about the pleasure of the process, but no - it’s about anticipation. Therefore, the rat with implanted electrodes from the famous 1954 experiment died not from pleasure, but from exhaustion in trying to get pleasure.
The pleasure of anticipation is necessary for people (and animals) to set goals for themselves and learn new things, because it is biologically justifiable. The more you can do, the more chances you have to survive.

And the insidiousness of the mechanism is that dopamine is synthesized in dreams without specific action. You lie on the couch, daydream, and dopamine creates the illusion of achieving your goal. It’s not enough to make a wish list - you need to do it. Otherwise - empty.
In any kind of addiction, the most unpleasant thing is the restructuring of the brain. By provoking dopamine releases, we overstimulate our brain and this leads to a loss of sensitivity and pleasure from ordinary things. Everything around you stops making you happy, you lose motivation to do ordinary things, and the joy of life disappears. This occurs due to a decrease in the number of dopamine receptors.

As with many drugs, consuming sugar results in a surge of dopamine. Over the long term, regular sugar consumption actually significantly alters gene expression and reduces the availability of dopamine receptors in the midbrain and frontal lobe. Specifically, sugar increases the concentration of the D1 type of nerve receptor, but decreases the concentration of another type of receptor, D2, which is an inhibitor. Regular consumption of sugar also inhibits the action of the dopamine transporter: this protein pumps dopamine out of the synapse and back into the neuron after an action potential.

In short, this means that frequent sugar consumption interferes with dopamine signaling, desensitizes brain pathways, and increases the amount of sugar needed to activate midbrain dopamine receptors. The brain becomes tolerant to sugar. A person has to consume it in ever-increasing quantities to get that “sweet high.”

How dopamine controls movement

The motor pyramidal system is responsible for conscious movements. There are bodies of neurons that generate impulses for commands to skeletal muscles. The extrapyramidal system is unconscious and does not obey our will. It is responsible for maintaining muscle tone, posture, facial expressions, plasticity of movements, regulates congenital and acquired automatic motor acts, ensures the establishment of muscle tone and maintaining body balance; regulates accompanying movements, for example, arm movements when walking. Extrapyramidal disorders with decreased dopamine

Poor posture

Restless legs syndrome

What happens when the dopamine system is disrupted?

The level of dopamine is a kind of energy supply for the body. Dopamine levels influence the activity of the frontal lobes.

• If the dopamine level is too low, then the frontal lobes do not have enough energy - all incoming signals seem to be noise, nothing interesting, there is no desire to act, everything is terribly boring.
• If the dopamine level is optimal, the frontal lobes clearly highlight the signal - what needs to be done, where to strive.
• If the level of dopamine is too high, then everything seems to be a signal, the brain is overstimulated, and the consciousness is deprived of the ability to act adequately.

When the dopamine system is disrupted, its restraining function weakens and a person secretes more prolactin and ACTH. Excess prolactin causes multiple reproductive, sexual, metabolic and psycho-emotional disorders in men and women. Libido drops, swelling appears, headaches, and fat increases. And excess ACTH contributes to a greater release of cortisol, which significantly increases sensitivity to stress and increases the risk of burnout, and increased ACTH creates an anxious, melancholy, frightening emotional background and increases the risk of depression. Interestingly, people with drug addictions can often be recognized by elevated levels of prolactin and ACTH (Neuroendocrinology. 2003 Sep;78(3):154-62. Treatment-seeking inpatient cocaine abusers show hypothalamic dysregulation of both basal prolactin and cortisol secretion).

Under the name “dopamine” lies a very special substance - it is both a full-fledged hormone and a neurotransmitter. Due to its unique effect on the human body, dopamine (or dopamine) has become known as the hormone of joy, pleasure and love, but in medicine this drug is used to treat the most dangerous pathologies. Including life-threatening ones.

Mechanism of action of dopamine

Dopamine is produced in various parts of the body. The midbrain, immune cells, kidneys, etc. are responsible for the synthesis of the neurotransmitter hormone.

In order for all the dopamine that is synthesized in these areas to begin its work, special receptors are needed. There are 5 types of such dopamine receptors: DRD1, DRD2, DRD3, DRD4 and DRD5. D1 and D5 form a single group - when combined with them, dopamine activates cellular activity. When interacting with three other receptors, on the contrary, it reduces activity. The behavior of cells, in turn, directly affects the behavior and condition of a person.

After connecting with receptors, dopamine continues to move along one of three pathways:

1. The mesolimbic canal runs from the VTA (ventral tegmental area, midbrain) to the limbic system. Here dopamine forms emotions, feelings and desires.
2. The mesocortical pathway runs from the VTA to the frontal cortex. Here the neurotransmitter affects those areas that are responsible for thinking, motivation and emotions.
3. The nigrostriatal pathway connects the substantia nigra of the midbrain with the striatum of the telencephalon. Dopamine receptors, which are responsible for motor activity, move along this path.

Individual dopamine receptors are distributed in peripheral organs and blood. By combining with them, the substance acts as a hormone: dilates blood vessels, increases blood flow, affects the synthesis of other hormones, etc.

How does a person feel when dopamine levels increase?

The level of natural dopamine in the blood invariably jumps if a situation that is pleasant for a person arises. Or if he is only anticipating the pleasure of such a situation.

When the brain receives a command that joy and pleasure are expected, hormone synthesis occurs instantly, and within a split second dopamine receptors are already rushing from the midbrain along their “paths.”

But the exact time at which such natural doping affects the body is still unknown. Dopamine can act all the time while a pleasant process continues (making love, a romantic walk, delicious tea, making a toy with a child, presenting a diploma). Or it can make a person happy with just a short memory.

The feeling of increased dopamine cannot be confused with anything. The first signs of action resemble the influence of adrenaline, but to a lesser extent: the pulse quickens, the heart begins to beat faster, and blood rushes to the skin. Attention increases, concentration increases, and the brain begins to work purposefully. But the main thing is that a person feels incredible euphoria, pleasure, delight and bliss.

How to artificially increase dopamine levels

A normal level of dopamine in the blood is the key to a fulfilling life. When enough dopamine is synthesized, we fall in love, enjoy new discoveries, think actively and do what we love. When the level of the neurotransmitter hormone drops, it leads to apathy and even depression.

Therefore, at all times, people have been tirelessly tormented by the question of how to increase dopamine levels naturally. And scientists have found several ways:

• Eat foods rich in tyrosine (dopamine is synthesized from it). These are bananas, avocados, almonds, beans, etc.
• Include vegetables and fruits with antioxidants in your diet. These are cabbage, spinach, bell peppers, prunes, oranges, spices, etc.
• Get enough sleep and exercise daily (at least morning exercises).
• Have sex regularly with your loved one.
• Take vitamin B6 and L-phenylalanine.

All of these methods are quite gentle, but there are also more aggressive methods of increasing the dopamine surge. These include any prohibited substances (synthetic and herbal drugs). Different drugs act differently, but the essence is the same - artificial stimulation of the brain occurs, which can lead to irreversible consequences. In addition to their physical and mental devastation, drugs condition the brain to such stimulation. As a result, dopamine receptors die, and less and less of the “native” hormone is produced in the body.

Dopamine in medicine

Artificial dopamine is also successfully used in medicine. When the dopamine drug enters the blood, it instantly dilates the blood vessels of the heart and kidneys, increases cardiac and renal blood flow and the excretion of sodium in the urine. This effect reduces the load on the heart.

In connection with this action, the list of indications for which dopamine is required is quite narrow. This:

• shock (cardiogenic, traumatic, septic, etc.);
• acute renal failure;
• severe heart failure;
• open heart surgery.

Artificial dopamine comes under a variety of names. "Alphamet", "Cardosteril", "Hydroxytyramine", "Dinatra", "Dopamex", "Intropin", "Dopmin", "Methyldop", "Presolizin", "Aprical", "Revivan", "Dofan" and "Dopamine" “—that’s all it is, the neurotransmitter hormone dopamine.

Application and side effects

Dopamine is taken exclusively intravenously, the main thing for the doctor when prescribing is precise dosage.

A minimal excess of the dopamine dose can cause serious side effects. These are nausea and vomiting, tachycardia and heart rhythm disturbances, angina pectoris, headache, blood pressure surges, vascular spasms. With long-term use of dopamine, rare cases of gangrene of the fingers (both arms and legs) have been recorded.

Each dopamine dose is selected individually, and the patient’s condition must be monitored using hemodynamics and an electrocardiogram. In case of hypovolemic shock, dopamine injections must be combined with an infusion of plasma or plasma substitutes.

The neurotransmitter hormone is produced in ampoules; for injection, it is diluted in a 5% glucose solution or isotonic sodium chloride solution. Dosage – 25 or 200 mg of hormonal drug per 125 or 400 ml. Initially, the rate of administration is 1-5 mcg/kg per minute; if required, it can be increased to 10-25 mcg/kg per minute. Course – continuously from 2-3 hours 1-4 days. The maximum daily dose should not exceed 800 mg. Synthetic dopamine acts immediately after entering the blood, and the effect stops 5-10 minutes after the end of the procedure.

Scientific experiments with dopamine

One of the most important roles of the neurotransmitter dopamine is its participation in the reward system and providing pleasure.

The first historically important experiment with dopamine was carried out in 1954 - Canadian researchers James Olds and Peter Milner conducted an experiment with rats who were implanted with electrodes in the midbrain and taught to press a lever that delivered a minimal discharge of current directly to the brain. Having understood what was happening, the rats managed to press the lever up to 1000 times per hour. This allowed scientists to assume that in the midbrain lies a powerful pleasure center, controlled by the hormone dopamine.

But in 1997, Cambridge scientist Wolfram Schultz proved to the world that dopamine works much more subtly. His experiment involved monkeys who formed a conditioned reflex - after a light signal, various portions of juice were injected.

It turned out that dopamine activity was higher when the portion of juice was unexpectedly large and when the treat was given without warning. At the stage of reflex formation, it was already noticed that the dopamine surge is strongest after the signal, but before the portion of juice. And when the treat was not given after the signal, the activity of the neurotransmitter dropped sharply.

All these facts helped to conclude that dopamine determines the formation of a positive feeling even at the stage of anticipation of a reward and helps to form a conditioned reflex. If there is no reward, the brain gradually eliminates this situation from memory - the low level of the pleasure hormone clearly indicates this.

In the brain, which, as people like to say, is “washed with chemical elements,” one of them seems to occupy a special position. Dopamine is the molecule behind all of our most sensual behaviors and secret, passionate desires. Dopamine is love. Dopamine is lust. Dopamine is adultery. Dopamine is motivation. Dopamine is attention. Dopamine is feminism. Dopamine is bad habits.

Yes, dopamine has a lot of work to do.

Dopamine is one of the neurotransmitters that everyone seems to know everything about. Vaughn Bell once called it the Kim Kardashian of molecules, but I don't think that's true of dopamine. Suffice it to say that dopamine is a big thing. And almost every week there are new articles about dopamine.

So dopamine is your craving for small cupcakes? Passion for gambling? Your alcoholism? Your sex life? The reality is that dopamine has something to do with all of the above. Dopamine is a chemical in your body. That's all. But this does not make the situation with him any simpler.

So what is dopamine? Dopamine is one of the chemical signals that transmits information from one neuron to another over a tiny distance that separates them from each other. When a signal leaves one neuron, it enters the space (synapse) between the two neurons and encounters receptors on the other side that pick it up, sending a signal to the receiving neuron. This all seems very simple, but if you increase the number from one pair of neurons to a huge network of them in your brain, then the situation becomes very complex very quickly. The impact of a dopamine release depends on where it comes from, what neurons it deals with, what receptors pick up dopamine (there are five known types), and what role the sending and receiving neurons play in it.

And dopamine has enough to do! He takes part in the operation of a large number of important routes. But when most people talk about dopamine, especially when it comes to motivation, addictions, attention or lust, they are talking about the dopamine pathways known as the mesolimbic pathways, which originate from a cell in the ventral tegmental area, tucked away in the very center of the brain. , and through which their projections are transmitted to places such as the nucleus accumbens and its cortex. Increased release of dopamine in the core of the brain occurs as a result of sex, drugs and rock and roll. And the dopamine signal transmitted to these areas changes during drug use. All types of harmful drug addictions, from alcohol to cocaine, increase the amount of dopamine in these areas to varying degrees, and many people like to refer to the dopamine surge as “motivation” or “pleasure.” But it is not so. In reality, dopamine signals the presence of feedback regarding perceived pleasure. If you, say, associate a stimulus (such as a glass pipe) with a hit of cocaine, then you will begin to increase the amount of dopamine in the core of your brain in response to one type of pipe, as your brain predicts the reward. But if you don’t get your dose in such a situation, the amount of dopamine may decrease, and this is not the most pleasant feeling. So you might think that dopamine is probably a predictor of reward. But again I would like to repeat that in reality everything is much more complicated. For example, the amount of dopamine in the core of the brain may increase in people suffering from post-traumatic stress and experiencing hyperarousal or paranoia. So you can say that, at least in this part of the brain, dopamine is not an addiction, a reward, or a fear. This is rather what we call salience. Salience is more than attention: it is an indicator of the existence of something worth paying attention to or something special. This may be part of the mesolimbic role in attention deficit hyperactivity disorder, as well as part of the role in addictions.

What about dopamine itself? It is not salience. It plays many more roles in the human brain. For example, dopamine plays an important role in initial movement, and the destruction of dopamine neurons in a part of the brain called the substantia nigra gives rise to certain symptoms that occur in Parkinson's disease. Dopamine also plays an important role as a hormone and inhibits the action of prolactin, thus preventing the formation of breast milk. Once again in the mesolimbic pathways, dopamine may play a role in psychosis, and many antipsychotic drugs for schizophrenia target dopamine. In the frontal cortex, dopamine is involved in executive functions such as attention. In other parts of the body, dopamine affects nausea, kidney function, and heart function.

With all these wonderful qualities of dopamine, I find the simplistic view of dopamine as “attention” or an “addiction” to be incredibly annoying. It's so easy to say that dopamine is X and be done with the subject. This is comforting. There is a feeling that you have learned the truth at some fundamental biological level, and that’s the end of it. And there will always be enough scientific papers describing the action of dopamine in area X to support your belief. However, a simplistic view of dopamine, or any other chemical in the brain, down to a single action or outcome, gives people a false impression of what the brain does. If you think that dopamine is motivation, then the more of it, the better, right? Not at all necessary! Because dopamine still represents “pleasure” or a “high”, and therefore too much of it is too much. If you believe that dopamine is primarily associated with pleasure or attention, you will end up with a misconception about some of the problems that dopamine causes, including addictions and attention deficit hyperactivity disorder, and you will develop a misconception about on how to deal with them.

There's another reason I don't like all this "dopamine is mania" talk, because this kind of simplistic approach doesn't allow us to see the miracle of dopamine. If you are sure that “dopamine is there,” then you may get the impression that you have already figured it all out. And you will be surprised by the fact that we have not yet solved all the problems with addictions. Complexity means that diseases associated with dopamine (or other chemicals or parts of the brain, for that matter) are often difficult to understand and even more difficult to treat.

I keep emphasizing the complexity of dopamine, and as a result it may seem like I'm taking some of the glamor and sex appeal away from it. But I don't think so. It's the complexity of how neurotransmitters work that makes it so amazing. It is the simplicity of the individual molecule and its receptors that makes dopamine so flexible that it allows the resulting system to be so complex. And this doesn't just apply to dopamine. Dopamine has only five types of receptors, while another neurotransmitter, serotonin, has already been discovered to have 14, and there is reason to believe that there may be even more. Other neurotransmitters have receptors with different subtypes, all of which act in different locations, where any combination can create a different effect than the others. There are many types of neurons, and they have trillions and trillions of connections. And thanks to all this, you have the opportunity to want, talk, eat, fall in love, get married, get divorced, become addicted to cocaine and one day overcome your addiction. If you imagine the number of connections required simply for you to read and understand a given sentence - from the eyes to the brain, then processing, comprehension, to the movement of the fingers turning the page - then you begin to feel a sense of awe. Our brain can do all of this, although sometimes it makes us think about pepperoni pizza or what the message you received from your girlfriend might actually mean. It is this complexity that makes the brain so fascinating and amazing.

So dopamine must have something to do with addictions - both little cupcakes and cocaine. It must have to do with lust and love. It must be related to milk. It must be related to movement, motivation, attention, psychosis. Dopamine plays a role in all of this. But at the same time, he is not anything from this list, and we should not wish for it. Its complexity is what makes it so amazing. It shows us what the brain can do with one single molecule.

InoSMI materials contain assessments exclusively of foreign media and do not reflect the position of the InoSMI editorial staff.