File Name: neurotransmitters drugs and brain function .zip
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These target cells may be in glands, muscles, or other neurons. Billions of neurotransmitter molecules work constantly to keep our brains functioning, managing everything from our breathing to our heartbeat to our learning and concentration levels. They can also affect a variety of psychological functions such as fear, mood, pleasure, and joy.
Dopamine DA , a contraction of 3,4- d ihydr o xy p henethyl amine is a neurotransmitter that plays several important roles in the brain and body. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical , L-DOPA , which is synthesized in the brain and kidneys.
Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter —a chemical released by neurons nerve cells to send signals to other nerve cells.
The brain includes several distinct dopamine pathways , one of which plays a major role in the motivational component of reward-motivated behavior. The anticipation of most types of rewards increases the level of dopamine in the brain,  and many addictive drugs increase dopamine release or block its reuptake into neurons following release. Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones.
These pathways and cell groups form a dopamine system which is neuromodulatory. In popular culture and media, dopamine is usually seen as the main chemical of pleasure, but the current opinion in pharmacology is that dopamine instead confers motivational salience ;    in other words, dopamine signals the perceived motivational prominence i. Outside the central nervous system, dopamine functions primarily as a local paracrine messenger.
In blood vessels, it inhibits norepinephrine release and acts as a vasodilator at normal concentrations ; in the kidneys, it increases sodium excretion and urine output; in the pancreas, it reduces insulin production; in the digestive system, it reduces gastrointestinal motility and protects intestinal mucosa ; and in the immune system, it reduces the activity of lymphocytes. With the exception of the blood vessels, dopamine in each of these peripheral systems is synthesized locally and exerts its effects near the cells that release it.
Several important diseases of the nervous system are associated with dysfunctions of the dopamine system, and some of the key medications used to treat them work by altering the effects of dopamine.
Parkinson's disease , a degenerative condition causing tremor and motor impairment, is caused by a loss of dopamine-secreting neurons in an area of the midbrain called the substantia nigra. There is evidence that schizophrenia involves altered levels of dopamine activity, and most antipsychotic drugs used to treat this are dopamine antagonists which reduce dopamine activity.
Restless legs syndrome and attention deficit hyperactivity disorder ADHD are associated with decreased dopamine activity. Dopamine itself is available as a manufactured medication for intravenous injection : although it cannot reach the brain from the bloodstream , its peripheral effects make it useful in the treatment of heart failure or shock , especially in newborn babies.
A dopamine molecule consists of a catechol structure a benzene ring with two hydroxyl side groups with one amine group attached via an ethyl chain.
Like most amines, dopamine is an organic base. Dopamine is synthesized in a restricted set of cell types, mainly neurons and cells in the medulla of the adrenal glands. The direct precursor of dopamine, L -DOPA , can be synthesized indirectly from the essential amino acid phenylalanine or directly from the non-essential amino acid tyrosine. Although dopamine is also found in many types of food, it is incapable of crossing the blood—brain barrier that surrounds and protects the brain.
L -Phenylalanine is converted into L -tyrosine by the enzyme phenylalanine hydroxylase , with molecular oxygen O 2 and tetrahydrobiopterin as cofactors. Dopamine itself is used as precursor in the synthesis of the neurotransmitters norepinephrine and epinephrine.
Some of the cofactors also require their own synthesis. In clinical research on schizophrenia, measurements of homovanillic acid in plasma have been used to estimate levels of dopamine activity in the brain. A difficulty in this approach however, is separating the high level of plasma homovanillic acid contributed by the metabolism of norepinephrine. Although dopamine is normally broken down by an oxidoreductase enzyme, it is also susceptible to oxidation by direct reaction with oxygen, yielding quinones plus various free radicals as products.
Quinones and free radicals produced by autoxidation of dopamine can poison cells , and there is evidence that this mechanism may contribute to the cell loss that occurs in Parkinson's disease and other conditions. Dopamine exerts its effects by binding to and activating cell surface receptors. Inside the brain, dopamine functions as a neurotransmitter and neuromodulator , and is controlled by a set of mechanisms common to all monoamine neurotransmitters.
In most cases, the release of dopamine occurs through a process called exocytosis which is caused by action potentials , but it can also be caused by the activity of an intracellular trace amine-associated receptor , TAAR1. Once in the synapse, dopamine binds to and activates dopamine receptors.
They are then absorbed back into the presynaptic cell, via reuptake mediated either by the dopamine transporter or by the plasma membrane monoamine transporter. In the brain the level of extracellular dopamine is modulated by two mechanisms: phasic and tonic transmission.
Inside the brain, dopamine plays important roles in executive functions , motor control , motivation , arousal , reinforcement , and reward , as well as lower-level functions including lactation , sexual gratification , and nausea. The dopaminergic cell groups and pathways make up the dopamine system which is neuromodulatory. Dopaminergic neurons dopamine-producing nerve cells are comparatively few in number—a total of around , in the human brain  —and their cell bodies are confined in groups to a few relatively small brain areas.
The dopaminergic areas they identified are the substantia nigra groups 8 and 9 ; the ventral tegmental area group 10 ; the posterior hypothalamus group 11 ; the arcuate nucleus group 12 ; the zona incerta group 13 and the periventricular nucleus group The substantia nigra is a small midbrain area that forms a component of the basal ganglia. This has two parts—an input area called the pars compacta and an output area the pars reticulata. The dopaminergic neurons are found mainly in the pars compacta cell group A8 and nearby group A9.
The ventral tegmental area VTA is another midbrain area. The most prominent group of VTA dopaminergic neurons projects to the prefrontal cortex via the mesocortical pathway and another smaller group projects to the nucleus accumbens via the mesolimbic pathway.
Together, these two pathways are collectively termed the mesocorticolimbic projection. The posterior hypothalamus has dopamine neurons that project to the spinal cord, but their function is not well established. The arcuate nucleus and the periventricular nucleus of the hypothalamus have dopamine neurons that form an important projection—the tuberoinfundibular pathway which goes to the pituitary gland , where it influences the secretion of the hormone prolactin.
The zona incerta, grouped between the arcuate and periventricular nuclei, projects to several areas of the hypothalamus, and participates in the control of gonadotropin-releasing hormone , which is necessary to activate the development of the male and female reproductive systems , following puberty. An additional group of dopamine-secreting neurons is found in the retina of the eye.
The largest and most important sources of dopamine in the vertebrate brain are the substantia nigra and ventral tegmental area. Progress in understanding the functions of the basal ganglia has been slow. In other words, they essentially form a decision-making system. The basal ganglia can be divided into several sectors, and each is involved in controlling particular types of actions. Dopamine contributes to the action selection process in at least two important ways.
First, it sets the "threshold" for initiating actions. The second important effect of dopamine is as a "teaching" signal. In the language used to discuss the reward system, reward is the attractive and motivational property of a stimulus that induces appetitive behavior also known as approach behavior and consummatory behavior.
Within the brain, dopamine functions partly as a global reward signal. An initial dopamine response to a rewarding stimulus encodes information about the salience , value, and context of a reward. Evidence from microelectrode recordings from the brains of animals shows that dopamine neurons in the ventral tegmental area VTA and substantia nigra are strongly activated by a wide variety of rewarding events. While dopamine has a central role in causing "wanting," associated with the appetitive or approach behavioral responses to rewarding stimuli, detailed studies have shown that dopamine cannot simply be equated with hedonic "liking" or pleasure, as reflected in the consummatory behavioral response.
These produce increases in "wanting" behaviors, but do not greatly alter expressions of pleasure or change levels of satiation. Dopamine does not cross the blood—brain barrier, so its synthesis and functions in peripheral areas are to a large degree independent of its synthesis and functions in the brain.
The relatively small quantity of unconjugated dopamine in the bloodstream may be produced by the sympathetic nervous system , the digestive system, or possibly other organs. Beyond its role in modulating blood flow, there are several peripheral systems in which dopamine circulates within a limited area and performs an exocrine or paracrine function. In the immune system dopamine acts upon receptors present on immune cells, especially lymphocytes.
The functional significance of this system is unclear, but it affords a possible route for interactions between the nervous system and immune system, and may be relevant to some autoimmune disorders.
The renal dopaminergic system is located in the cells of the nephron in the kidney, where all subtypes of dopamine receptors are present. Its actions include increasing the blood supply to the kidneys, increasing the glomerular filtration rate , and increasing the excretion of sodium in the urine. Hence, defects in renal dopamine function can lead to reduced sodium excretion and consequently result in the development of high blood pressure. There is strong evidence that faults in the production of dopamine or in the receptors can result in a number of pathologies including oxidative stress , edema , and either genetic or essential hypertension.
Oxidative stress can itself cause hypertension. In the pancreas the role of dopamine is somewhat complex. The pancreas consists of two parts, an exocrine and an endocrine component. The exocrine part synthesizes and secretes digestive enzymes and other substances, including dopamine, into the small intestine.
The pancreatic islets make up the endocrine part of the pancreas, and synthesize and secrete hormones including insulin into the bloodstream. Dopamine as a manufactured medication is sold under the trade names Intropin, Dopastat, and Revimine, among others. It is especially important in treating these in newborn infants. Since the half-life of dopamine in plasma is very short—approximately one minute in adults, two minutes in newborn infants and up to five minutes in preterm infants—it is usually given in a continuous intravenous drip rather than a single injection.
Its effects, depending on dosage, include an increase in sodium excretion by the kidneys, an increase in urine output, an increase in heart rate , and an increase in blood pressure.
Side effects of dopamine include negative effects on kidney function and irregular heartbeats. A fluorinated form of L-DOPA known as fluorodopa is available for use in positron emission tomography to assess the function of the nigrostriatal pathway.
The dopamine system plays a central role in several significant medical conditions, including Parkinson's disease, attention deficit hyperactivity disorder, Tourette syndrome , schizophrenia , bipolar disorder , and addiction.
Aside from dopamine itself, there are many other important drugs that act on dopamine systems in various parts of the brain or body. Some are used for medical or recreational purposes, but neurochemists have also developed a variety of research drugs, some of which bind with high affinity to specific types of dopamine receptors and either agonize or antagonize their effects, and many that affect other aspects of dopamine physiology,  including dopamine transporter inhibitors, VMAT inhibitors, and enzyme inhibitors.
A number of studies have reported an age-related decline in dopamine synthesis and dopamine receptor density i. Other neurotransmitters, such as serotonin and glutamate also show a decline in output with aging. Studies reported that dopamine imbalance influences the fatigue in multiple sclerosis. Parkinson's disease is an age-related disorder characterized by movement disorders such as stiffness of the body, slowing of movement, and trembling of limbs when they are not in use.
The most widely used treatment for parkinsonism is administration of L-DOPA, the metabolic precursor for dopamine. L-DOPA treatment cannot restore the dopamine cells that have been lost, but it causes the remaining cells to produce more dopamine, thereby compensating for the loss to at least some degree.
Dopaminergic medications that are used to treat Parkinson's disease are sometimes associated with the development of a dopamine dysregulation syndrome , which involves the overuse of dopaminergic medication and medication-induced compulsive engagement in natural rewards like gambling and sexual activity.
Cocaine , substituted amphetamines including methamphetamine , Adderall , methylphenidate marketed as Ritalin or Concerta , and other psychostimulants exert their effects primarily or partly by increasing dopamine levels in the brain by a variety of mechanisms.
The effects of psychostimulants include increases in heart rate, body temperature, and sweating; improvements in alertness, attention, and endurance; increases in pleasure produced by rewarding events; but at higher doses agitation, anxiety, or even loss of contact with reality. A variety of addictive drugs produce an increase in reward-related dopamine activity.
For other addictive drugs such as the opioid heroin, the increased levels of dopamine in the reward system may play only a minor role in addiction.
The dopamine system plays a crucial role in several aspects of addiction. At the earliest stage, genetic differences that alter the expression of dopamine receptors in the brain can predict whether a person will find stimulants appealing or aversive.
Dopamine DA , a contraction of 3,4- d ihydr o xy p henethyl amine is a neurotransmitter that plays several important roles in the brain and body. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical , L-DOPA , which is synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter —a chemical released by neurons nerve cells to send signals to other nerve cells. The brain includes several distinct dopamine pathways , one of which plays a major role in the motivational component of reward-motivated behavior.
Neurotransmitters, Drugs and Brain Function aims to link basic aspects of the activity of neurotransmitters at the receptor and synaptic level with their role in normal brain function, disease states, and drug action. Thus, the material considers to what extent our knowledge of the central synaptic action of certain drugs can explain their possible roles in the cause of diseases and in the modes of action of drugs effective in those conditions. It offers a working explanation of drug and neurotransmitter action in CNS function, with a clear, comprehensive, and challenging style of writing. The authors review the chemical basis for drugs and the conditions they treat. It also, includes numerous illustrations and schematic diagrams. This book aims to cover the role of neurotransmitters, the substances released form neurons to act on neurons. It covers what they do, how they do it and how their activity is involved in brain function and affected by drugs and disease.
Neurotransmitters are chemical messengers in the body. Their job is to transmit signals from nerve cells to target cells. These target cells may be in muscles, glands, or other nerves. Nerve cells, also known as neurons, and their neurotransmitters play important roles in this system. Nerve cells fire nerve impulses. They do this by releasing neurotransmitters, which are chemicals that carry signals to other cells.
PDF | On Jan 1, , John S Duncan published Neurotransmitters, drugs and brain function | Find, read and cite all the research you need on.
Positron emission tomography PET is a non-invasive imaging technique used to assess various brain functions, including cerebral blood flow, glucose metabolism, and neurotransmission, in the living human brain. In particular, neurotransmission mediated by the monoamine neurotransmitters dopamine, serotonin, and norepinephrine, has been extensively examined using PET probes, which specifically bind to the monoamine receptors and transporters.
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