Dopamine
Encyclopedia
Dopamine is a catecholamine
neurotransmitter
present in a wide variety of animals, including both vertebrates and invertebrates. In the brain
, this substituted phenethylamine
functions as a neurotransmitter
, activating the five known types of dopamine receptor
s—D1, D2, D3, D4, and D5—and their variants. Dopamine is produced in several areas of the brain, including the substantia nigra
and the ventral tegmental area. Dopamine is also a neurohormone
released by the hypothalamus
. Its main function as a hormone is to inhibit the release of prolactin
from the anterior lobe of the pituitary.
Dopamine is available as an intravenous medication
acting on the sympathetic
nervous system
, producing effects such as increased heart rate
and blood pressure
. However, because dopamine cannot cross the blood-brain barrier
, dopamine given as a drug does not directly affect the central nervous system
. To increase the amount of dopamine in the brains of patients with diseases such as Parkinson's disease
and dopa-responsive dystonia
, L-DOPA (the precursor of dopamine) is often given because it crosses the blood-brain barrier relatively easily.
and Nils-Åke Hillarp at the Laboratory for Chemical Pharmacology of the National Heart Institute of Sweden
. Carlsson was awarded the 2000 Nobel Prize in Physiology or Medicine
for showing that dopamine is not only a precursor of norepinephrine
(noradrenaline) and epinephrine
(adrenaline), but also a neurotransmitter.
of 2-(3,4-dimethoxyphenyl)ethylamine (left) using hydrogen bromide
.
family, dopamine is a precursor to norepinephrine
(noradrenaline) and then epinephrine
(adrenaline) in the biosynthetic pathways for these neurotransmitters.
of the adrenal gland
s) first by the hydroxylation of the amino acid L-tyrosine to L-DOPA via the enzyme tyrosine 3-monooxygenase, also known as tyrosine hydroxylase
, and then by the decarboxylation
of L-DOPA by aromatic L-amino acid decarboxylase
(which is often referred to as dopa decarboxylase). In some neurons, dopamine is further processed into norepinephrine
by dopamine beta-hydroxylase.
In neuron
s, dopamine is packaged after synthesis into vesicles
, which are then released into the synapse
in response to a presynaptic action potential
.
and basal ganglia
, dopamine is inactivated by reuptake
via the dopamine transporter
(DAT1), then enzymatic breakdown by monoamine oxidase
(MAOA and MAOB) into 3,4-dihydroxyphenylacetic acid. In the prefrontal cortex, however, there are very few dopamine transporter proteins, and dopamine is instead inactivated by reuptake via the norepinephrine transporter
(NET), presumably on neighboring norepinephrine neurons, then enzymatic breakdown by catechol-O-methyl transferase
(COMT) into 3-methoxytyramine
. The DAT1 pathway is roughly an order of magnitude faster than the NET pathway: in mice, dopamine concentrations decay with a half-life of 200 ms in the caudate nucleus (which uses the DAT1 pathway) versus 2,000 ms in the prefrontal cortex. Dopamine that is not broken down by enzymes is repackaged into vesicles for reuse by VMAT2
.
Dopamine has many functions in the brain, including important roles in behavior and cognition
, voluntary movement
, motivation
, punishment
and reward
, inhibition of prolactin
production (involved in lactation
and sexual gratification), sleep
, mood
, attention
, working memory
, and learning
. Dopaminergic neurons (i.e., neurons whose primary neurotransmitter is dopamine) are present chiefly in the ventral tegmental area (VTA) of the midbrain, the substantia nigra pars compacta
, and the arcuate nucleus
of the hypothalamus.
It has been hypothesized that dopamine transmits reward prediction error, although this has been questioned. According to this hypothesis, the phasic responses of dopamine neurons are observed when an unexpected reward is presented. These responses transfer to the onset of a conditioned stimulus
after repeated pairings with the reward. Further, dopamine neurons are depressed when the expected reward is omitted. Thus, dopamine neurons seem to encode the prediction error of rewarding outcomes. In nature, we learn to repeat behaviors that lead to maximizing rewards. Dopamine is therefore believed to provide a teaching signal to parts of the brain responsible for acquiring new behavior. Temporal difference learning
provides a computational model describing how the prediction error of dopamine neurons is used as a teaching signal.
The reward system in insects uses octopamine
, which is the presumed arthropod homolog of norepinephrine
, rather than dopamine. In insects, dopamine acts instead as a punishment signal and is necessary to form aversive memories.
neurons form a neurotransmitter system which originates in substantia nigra pars compacta, ventral tegmental area (VTA), and hypothalamus
. These project axon
s to large areas of the brain which are typically divided into four major pathways:
This innervation explains many of the effects of activating this dopamine system. For instance, the mesolimbic pathway
connects the VTA and nucleus accumbens
; both are central to the brain reward system
.
Whilst the distinction between pathways is widely used, and is regarded as a “convenient heuristic when considering the dopamine system”, it is not absolute, and there is some overlap in the projection targets of each group of neurons.
activity of single spikes, and rapid bursts of typically 2-6 spikes in quick succession. Concentrated bursts of activity result in a greater increase of extracellular dopamine levels than would be expected from the same number of spikes distributed over a longer period of time.
and norepinephrine transporter
blocker that competitively inhibits dopamine uptake to increase the lifetime of dopamine and augments an overabundance of dopamine (an increase of up to 150 percent) within the parameters of the dopamine neurotransmitters. Like cocaine, amphetamines increase the concentration of dopamine in the synaptic
gap, but by a different mechanism. Amphetamines and methamphetamine
are similar in structure to dopamine, and so can enter the terminal bouton of the presynaptic neuron via its dopamine transporters as well as by diffusing through the neural membrane directly. By entering the presynaptic neuron, amphetamines force dopamine molecules out of their storage vesicles
and expel them into the synaptic gap by making the dopamine transporters work in reverse.
. Insufficient dopamine biosynthesis
in the dopaminergic neurons can cause Parkinson's disease
, a condition in which one loses the ability to execute smooth, controlled movements.
from the anterior pituitary
gland. Dopamine produced by neurons in the arcuate nucleus
of the hypothalamus is secreted into the hypothalamo-hypophysial blood vessels of the median eminence
, which supply the pituitary gland
. The lactotrope cells that produce prolactin
, in the absence of dopamine, secrete prolactin continuously; dopamine inhibits this secretion. Thus, in the context of regulating prolactin secretion, dopamine is occasionally called prolactin-inhibiting factor (PIF), prolactin-inhibiting hormone (PIH), or prolactostatin.
s, dopamine controls the flow of information from other areas of the brain. Dopamine disorders in this region of the brain can cause a decline in neurocognitive
functions, especially memory
, attention
, and problem-solving. Reduced dopamine concentrations in the prefrontal cortex are thought to contribute to attention deficit disorder. It has been found that D1 receptors as well as D4 receptors are responsible for the cognitive-enhancing effects of dopamine, whereas D2 receptors are more specific for motor actions.
and vomiting via interactions in the chemoreceptor trigger zone
. Metoclopramide
is a D2-receptor antagonist that functions as a prokinetic/antiemetic
.
s) have been shown to impair concentration, reduce motivation, cause anhedonia
(inability to experience pleasure), and long-term use has been associated with tardive dyskinesia
, an irreversible movement disorder. Antipsychotics have significant effects on gonadal hormones including significantly lower levels of estradiol and progesterone in women whereas men display significantly lower levels of testosterone and DHEA when undergoing antipsychotic drug treatment compared to controls. Antipsychotics are known to cause hyperprolactinaemia
leading to amenorrhea, cessation of normal cyclic ovarian function, loss of libido, occasional hirsutism
, false positive pregnancy tests, and long-term risk of osteoporosis in women. The effects of hyperprolactinemia in men are gynaecomastia, lactation
, impotence, loss of libido
, and hypospermatogenesis
. Furthermore, antipsychotic drugs are associated with weight gain
, diabetes, drooling
, dysphoria
(abnormal depression and discontent), fatigue, sexual dysfunction
, heart rhythm
problems, stroke
and heart attack.
Selective D2/D3 agonists pramipexole
and ropinirole
, used to treat restless legs syndrome
(RLS), have limited anti-anhedonic properties as measured by the Snaith-Hamilton Pleasure Scale (SHAPS).
and cannabinoid transmission instead of dopamine may modulate consummatory pleasure and food palatability (liking).
This could explain why animals' "liking" of food is independent of brain dopamine concentration. Other consummatory pleasures, however, may be more associated with dopamine. One study found that both anticipatory and consummatory measures of sexual behavior (male rats) were disrupted by DA receptor antagonists.
Libido can be increased by drugs that affect dopamine, but not by drugs that affect opioid peptide
s or other neurotransmitters.
of the brain, providing feelings of enjoyment and reinforcement
to motivate a person proactively to perform certain activities. Dopamine is released (particularly in areas such as the nucleus accumbens
and prefrontal cortex
) by rewarding
experiences such as food
, sex, drugs
, and neutral stimuli
that become associated
with them. Recent studies indicate that aggression
may also stimulate the release of dopamine in this way.
This theory can be discussed in terms of drugs such as cocaine
, nicotine
, and amphetamine
s, which directly or indirectly lead to an increase of dopamine in the mesolimbic reward pathway
of the brain, and in relation to neurobiological theories of chemical addiction
(not to be confused with psychological dependence
), arguing that this dopamine pathway
is pathologically altered in addicted persons.
Dopaminergic neurons of the midbrain are the main source of dopamine in the brain. Dopamine has been shown to be involved in the control of movements, the signaling of error in prediction of reward, motivation, and cognition. Cerebral dopamine depletion is the hallmark of Parkinson's disease. Other pathological states have also been associated with dopamine dysfunction, such as schizophrenia, autism, and attention deficit hyperactivity disorder, as well as drug abuse.
Dopamine is closely associated with reward-seeking behaviors, such as approach, consumption, and addiction. Recent researches suggest that the firing of dopaminergic neurons is a motivational substance as a consequence of reward-anticipation. This hypothesis is based on the evidence that, when a reward is greater than expected, the firing of certain dopaminergic neurons increases, which consequently increases desire or motivation towards the reward. However, recent research finds that while some dopaminergic neurons react in the way expected of reward neurons, others do not and seem to respond in regard to unpredictability. This research finds the reward neurons predominate in the ventromedial region in the substantia nigra pars compacta as well as the ventral tegmental area. Neurons in these areas project mainly to the ventral striatum
and thus might transmit value-related information in regard to reward values. The nonreward neurons are predominate in the dorsolateral area of the substantia nigra pars compacta which projects to the dorsal striatum
and may relate to orienting behaviour. It has been suggested that the difference between these two types of dopaminergic neurons arises from their input: reward-linked ones have input from the basal forebrain
while the nonreward-related ones from the lateral habenula.
and neostriatum using 6-hydroxydopamine.
With this large reduction in dopamine, the rats would no longer eat by their own volition. The researchers then force-fed the rats food and noted whether they had the proper facial expressions indicating whether they liked or disliked it. The researchers of this study concluded that the reduction in dopamine did not reduce the rat's consummatory pleasure, only the desire to actually eat. In another study, mutant hyperdopaminergic (increased dopamine) mice show higher "wanting" but not "liking" of sweet rewards.
of potentially important stimuli, such as sources of reward or of danger. This hypothesis argues that dopamine assists decision-making by influencing the priority, or level of desire, of such stimuli to the person concerned.
Dopamine's role in experiencing pleasure has been questioned by several researchers. It has been argued that dopamine is more associated with anticipatory desire and motivation (commonly referred to as "wanting") as opposed to actual consummatory pleasure (commonly referred to as "liking").
increases general arousal
and goal directed behaviors and decreases latent inhibition
; all three effects increase the creative drive of idea generation. This has led to a three-factor model of creativity
involving the frontal lobe
s, the temporal lobe
s, and mesolimbic dopamine.
. Traits common to negative schizophrenia
(social withdrawal, apathy
, anhedonia
) are thought to be related to a hypodopaminergic state in certain areas of the brain. In instances of bipolar disorder
, manic
subjects can become hypersocial, as well as hypersexual. This is credited to an increase in dopamine, because mania can be reduced by dopamine-blocking antipsychotics.
processing in multiple levels of the central nervous system
including the spinal cord
, periaqueductal gray
(PAG), thalamus
, basal ganglia
, insular cortex
, and cingulate cortex
. Accordingly, decreased levels of dopamine have been associated with painful symptoms that frequently occur in Parkinson's disease
. Abnormalities in dopaminergic neurotransmission have also been demonstrated in painful clinical conditions, including burning mouth syndrome, fibromyalgia
, and restless legs syndrome
. In general, the analgesic capacity of dopamine occurs as a result of dopamine D2 receptor activation; however, exceptions to this exist in the PAG, in which dopamine D1 receptor activation attenuates pain presumably via activation of neurons involved in descending inhibition. In addition, D1 receptor activation in the insular cortex appears to attenuate subsequent pain-related behavior.
, and stimulant medications used to successfully treat the disorder increase dopamine neurotransmission, leading to decreased symptoms. Consistent with this hypothesis, dopaminergic pathways have a role in inhibitory action control and the inhibition of the tendency to make unwanted actions.
The long term use of levodopa
in Parkinson's disease
has been linked to dopamine dysregulation syndrome
.
, and later enhanced by changes in diet and other environmental and social factors beginning approximately 80,000 years ago. Under this theory, the "high-dopamine" personality is characterized by high intelligence, a sense of personal destiny, a religious/cosmic preoccupation, an obsession with achieving goals and conquests, an emotional detachment that in many cases leads to ruthlessness, and a risk-taking mentality. High levels of dopamine are proposed to underlie increased psychological disorders in industrialized societies. According to this hypothesis, a "dopaminergic society" is an extremely goal-oriented, fast-paced, and even manic society, "given that dopamine is known to increase activity levels, speed up our internal clocks and create a preference for novel over unchanging environments." In the same way that high-dopamine individuals lack empathy and exhibit a more masculine behavioral style, dopaminergic societies are "typified by more conquest, competition, and aggression than nurturance and communality." Although behavioral evidence and some indirect anatomical evidence (e.g., enlargement of the dopamine-rich striatum in humans) support a dopaminergic expansion in humans, there is still no direct evidence that dopamine levels are markedly higher in humans relative to other apes. However, recent discoveries about the sea-side settlements of early man may provide evidence of dietary changes consistent with this hypothesis.
and schizophrenia
. Increased dopaminergic functional activity, specifically in the mesolimbic pathway
, is found in schizophrenic individuals. However, decreased activity in another dopaminergic pathway, the mesocortical pathway
, may also be involved. The two pathways are thought to be responsible for differing sets of symptoms seen in schizophrenia. Antipsychotic
medication
s act largely as dopamine antagonists, inhibiting dopamine at the receptor
level, and thereby blocking the effects of the neurochemical in a dose-dependant manner. The older, so-called typical antipsychotics most commonly act on D2 receptors, while the atypical drugs
also act on D1, D3 and D4 receptors. The finding that drugs such as amphetamines, methamphetamine and cocaine, which can increase dopamine levels by more than tenfold, can temporarily cause psychosis, provides further evidence for this link.
and dopa-responsive dystonia
. It is typically co-administered with an inhibitor of peripheral decarboxylation (DDC, dopa decarboxylase), such as carbidopa
or benserazide
. Inhibitors of alternative metabolic route for dopamine by catechol-O-methyl transferase
are also used. These include entacapone
and tolcapone
.
line outside the central nervous system. The effects in this form are dose dependent.
s, moderate expression on neutrophils and eosinophils, and high expression on B cell
s and natural killer cell
s. The sympathetic innervation
of lymphoid tissues is dopaminergic, and increases during stress. Dopamine can also affect immune cells in the spleen
, bone marrow
, and blood circulation. In addition, dopamine can be synthesized and released by the immune cells themselves.
The effects of dopamine on immune cells depend upon their physiological state. While dopamine activates resting T cell
s, it inhibits them when they are activated. Disorders such as schizophrenia
and Parkinson's disease
, in which there are changes in brain dopamine receptors and dopamine signaling pathways, are also associated with altered immune functioning.
s (PPOs) are a family of enzymes responsible for the browning of fresh fruits and vegetables when they are cut or bruised. These enzymes use molecular oxygen
(O2) to oxidise
various 1,2-diphenols
to their corresponding quinone
s. The natural substrate for PPOs in banana
s is dopamine. The product of their oxidation, dopamine quinone, spontaneously oxidises to other quinones. The quinones then polymerise and condense with amino acid
s and protein
s to form brown pigments
known as melanin
s. The quinones and melanins derived from dopamine may help protect damaged fruit and vegetables against growth of bacteria
and fungi.
Catecholamine
Catecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...
neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
present in a wide variety of animals, including both vertebrates and invertebrates. In the brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
, this substituted phenethylamine
Substituted phenethylamine
The substituted phenethylamines are chemical compounds with the 2-phenethylamine chemical structure modified at the phenyl ring, sidechain, and/or amino group. Some of them are psychoactive drugs, including stimulants, psychedelics, opioids, and entactogens, which exert their effects primarily...
functions as a neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
, activating the five known types of dopamine receptor
Dopamine receptor
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....
s—D1, D2, D3, D4, and D5—and their variants. Dopamine is produced in several areas of the brain, including the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
and the ventral tegmental area. Dopamine is also a neurohormone
Neurohormone
A neurohormone is any hormone produced and released by neurons.Examples include:*Thyrotropin-releasing hormone *Gonadotropin-releasing hormone *Adrenocorticotropin-releasing hormone*Oxytocin*Antidiuretic hormone *Epinephrine...
released by the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
. Its main function as a hormone is to inhibit the release of prolactin
Prolactin
Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
from the anterior lobe of the pituitary.
Dopamine is available as an intravenous medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
acting on the sympathetic
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
, producing effects such as increased heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
and blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
. However, because dopamine cannot cross the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
, dopamine given as a drug does not directly affect the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
. To increase the amount of dopamine in the brains of patients with diseases such as Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
and dopa-responsive dystonia
Dystonia
Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...
, L-DOPA (the precursor of dopamine) is often given because it crosses the blood-brain barrier relatively easily.
History
Dopamine was first synthesized in 1910 by George Barger and James Ewens at Wellcome Laboratories in London, England. It was named dopamine because it is a monoamine whose precursor in the Barger-Ewens synthesis is 3,4-dihydroxyphenylalanine (levodopamine or L-DOPA). Dopamine's function as a neurotransmitter was first recognized in 1958 by Arvid CarlssonArvid Carlsson
Arvid Carlsson is a Swedish scientist who is best known for his work with the neurotransmitter dopamine and its effects in Parkinson's disease...
and Nils-Åke Hillarp at the Laboratory for Chemical Pharmacology of the National Heart Institute of Sweden
Sweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
. Carlsson was awarded the 2000 Nobel Prize in Physiology or Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...
for showing that dopamine is not only a precursor of norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
(noradrenaline) and epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
(adrenaline), but also a neurotransmitter.
Chemistry
Dopamine (right) has the chemical formula C6H3(OH)2-CH2-CH2-NH2. Its chemical name is "4-(2-aminoethyl)benzene-1,2-diol" and its abbreviation is "DA." As a medicinal agent, dopamine is synthesized by demethylationDemethylation
Demethylation is the chemical process resulting in the removal a of methyl group from a molecule.A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen atoms....
of 2-(3,4-dimethoxyphenyl)ethylamine (left) using hydrogen bromide
Hydrogen bromide
Hydrogen bromide is the diatomic molecule HBr. HBr is a gas at standard conditions. Hydrobromic acid forms upon dissolving HBr in water. Conversely, HBr can be liberated from hydrobromic acid solutions with the addition of a dehydration agent, but not by distillation. Hydrogen bromide and...
.
Classification
As a member of the catecholamineCatecholamine
Catecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...
family, dopamine is a precursor to norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
(noradrenaline) and then epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
(adrenaline) in the biosynthetic pathways for these neurotransmitters.
Biosynthesis
Dopamine is biosynthesized in the body (mainly by nervous tissue and the medullaAdrenal medulla
The adrenal medulla is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of cells that secrete epinephrine , norepinephrine , and a small amount of dopamine in response to...
of the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
s) first by the hydroxylation of the amino acid L-tyrosine to L-DOPA via the enzyme tyrosine 3-monooxygenase, also known as tyrosine hydroxylase
Tyrosine hydroxylase
Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine . It does so using tetrahydrobiopterin as a coenzyme. DOPA is a precursor for dopamine, which, in turn, is a precursor for norepinephrine ...
, and then by the decarboxylation
Decarboxylation
Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...
of L-DOPA by aromatic L-amino acid decarboxylase
Aromatic L-amino acid decarboxylase
Aromatic L-amino acid decarboxylase is a lyase enzyme.-Reactions:It catalyzes several different decarboxylation reactions:* L-DOPA to dopamine - a neurotransmitter* 5-HTP to serotonin - also a neurotransmitter...
(which is often referred to as dopa decarboxylase). In some neurons, dopamine is further processed into norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
by dopamine beta-hydroxylase.
In neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s, dopamine is packaged after synthesis into vesicles
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
, which are then released into the synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
in response to a presynaptic action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
.
Inactivation and degradation
Two major degradation pathways for dopamine exist. In most areas of the brain, including the striatumStriatum
The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...
and basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
, dopamine is inactivated by reuptake
Reuptake
Reuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....
via the dopamine transporter
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...
(DAT1), then enzymatic breakdown by monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...
(MAOA and MAOB) into 3,4-dihydroxyphenylacetic acid. In the prefrontal cortex, however, there are very few dopamine transporter proteins, and dopamine is instead inactivated by reuptake via the norepinephrine transporter
Norepinephrine transporter
The norepinephrine transporter , also known as solute carrier family 6 member 2 , is a protein that in humans is encoded by the SLC6A2 gene....
(NET), presumably on neighboring norepinephrine neurons, then enzymatic breakdown by catechol-O-methyl transferase
Catechol-O-methyl transferase
Catechol-O-methyltransferase is one of several enzymes that degrade catecholamines such as dopamine, epinephrine, and norepinephrine. In humans, catechol-O-methyltransferase protein is encoded by the COMT gene...
(COMT) into 3-methoxytyramine
3-Methoxytyramine
3-Methoxytyramine , also known as 3-methoxy-4-hydroxyphenethylamine, is a metabolite of the neurotransmitter dopamine formed by the introduction of a methyl group to dopamine by the enzyme catechol-O-methyl transferase...
. The DAT1 pathway is roughly an order of magnitude faster than the NET pathway: in mice, dopamine concentrations decay with a half-life of 200 ms in the caudate nucleus (which uses the DAT1 pathway) versus 2,000 ms in the prefrontal cortex. Dopamine that is not broken down by enzymes is repackaged into vesicles for reuse by VMAT2
VMAT2
The vesicular monoamine transporter 2 also known as solute carrier family 18 member 2 is a protein that in humans is encoded by the SLC18A2 gene...
.
Functions in the brain
Dopamine has many functions in the brain, including important roles in behavior and cognition
Cognition
In science, cognition refers to mental processes. These processes include attention, remembering, producing and understanding language, solving problems, and making decisions. Cognition is studied in various disciplines such as psychology, philosophy, linguistics, and computer science...
, voluntary movement
Animal locomotion
Animal locomotion, which is the act of self-propulsion by an animal, has many manifestations, including running, swimming, jumping and flying. Animals move for a variety of reasons, such as to find food, a mate, or a suitable microhabitat, and to escape predators...
, motivation
Motivation
Motivation is the driving force by which humans achieve their goals. Motivation is said to be intrinsic or extrinsic. The term is generally used for humans but it can also be used to describe the causes for animal behavior as well. This article refers to human motivation...
, punishment
Punishment
Punishment is the authoritative imposition of something negative or unpleasant on a person or animal in response to behavior deemed wrong by an individual or group....
and reward
Reward system
In neuroscience, the reward system is a collection of brain structures which attempts to regulate and control behavior by inducing pleasurable effects...
, inhibition of prolactin
Prolactin
Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
production (involved in lactation
Lactation
Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, however it predates mammals. In humans the process of feeding milk is called breastfeeding or nursing...
and sexual gratification), sleep
Sleep
Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...
, mood
Mood (psychology)
A mood is a relatively long lasting emotional state. Moods differ from emotions in that they are less specific, less intense, and less likely to be triggered by a particular stimulus or event....
, attention
Attention
Attention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....
, working memory
Working memory
Working memory has been defined as the system which actively holds information in the mind to do verbal and nonverbal tasks such as reasoning and comprehension, and to make it available for further information processing...
, and learning
Learning
Learning is acquiring new or modifying existing knowledge, behaviors, skills, values, or preferences and may involve synthesizing different types of information. The ability to learn is possessed by humans, animals and some machines. Progress over time tends to follow learning curves.Human learning...
. Dopaminergic neurons (i.e., neurons whose primary neurotransmitter is dopamine) are present chiefly in the ventral tegmental area (VTA) of the midbrain, the substantia nigra pars compacta
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
, and the arcuate nucleus
Arcuate nucleus
The arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence...
of the hypothalamus.
It has been hypothesized that dopamine transmits reward prediction error, although this has been questioned. According to this hypothesis, the phasic responses of dopamine neurons are observed when an unexpected reward is presented. These responses transfer to the onset of a conditioned stimulus
Classical conditioning
Classical conditioning is a form of conditioning that was first demonstrated by Ivan Pavlov...
after repeated pairings with the reward. Further, dopamine neurons are depressed when the expected reward is omitted. Thus, dopamine neurons seem to encode the prediction error of rewarding outcomes. In nature, we learn to repeat behaviors that lead to maximizing rewards. Dopamine is therefore believed to provide a teaching signal to parts of the brain responsible for acquiring new behavior. Temporal difference learning
Temporal difference learning
Temporal difference learning is a prediction method. It has been mostly used for solving the reinforcement learning problem. "TD learning is a combination of Monte Carlo ideas and dynamic programming ideas." TD resembles a Monte Carlo method because it learns by sampling the environment according...
provides a computational model describing how the prediction error of dopamine neurons is used as a teaching signal.
The reward system in insects uses octopamine
Octopamine
Octopamine is an endogenous biogenic amine that is closely related to norepinephrine, and has effects on the adrenergic and dopaminergic systems. It is also found naturally in numerous plants, including bitter orange. Biosynthesis of the D--enantiomer of octopamine is by β-hydroxylation of...
, which is the presumed arthropod homolog of norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
, rather than dopamine. In insects, dopamine acts instead as a punishment signal and is necessary to form aversive memories.
Anatomy
DopaminergicDopaminergic
Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
neurons form a neurotransmitter system which originates in substantia nigra pars compacta, ventral tegmental area (VTA), and hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
. These project axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s to large areas of the brain which are typically divided into four major pathways:
- Mesocortical pathwayMesocortical pathwayThe mesocortical pathway is a neural pathway that connects the ventral tegmentum to the cerebral cortex, particularly the frontal lobes. It is one of the four major dopamine pathways in the brain...
connects the ventral tegmental area to the frontal lobe of the pre-frontal cortex. Neurons with somasSoma (biology)The soma , or perikaryon , or cyton, is the bulbous end of a neuron, containing the cell nucleus. The word "soma" comes from the Greek σῶμα, meaning "body"; the soma of a neuron is often called the "cell body"...
in the ventral tegmental area project axons into the pre-frontal cortex. - Mesolimbic pathwayMesolimbic pathwayThe mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex...
carries dopamine from the ventral tegmental area to the nucleus accumbensNucleus accumbensThe nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...
via the amygdalaAmygdalaThe ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
and hippocampusHippocampusThe hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
. The somas of the projecting neurons are in the ventral tegmental area. - Nigrostriatal pathwayNigrostriatal pathwayThe nigrostriatal pathway is a neural pathway that connects the substantia nigra with the striatum. It is one of the four major dopamine pathways in the brain, and is particularly involved in the production of movement, as part of a system called the basal ganglia motor loop.Loss of dopamine...
runs from the substantia nigra to the neostriatum. Somas in the substantia nigra project axons into the caudate nucleusCaudate nucleusThe caudate nucleus is a nucleus located within the basal ganglia of the brains of many animal species. The caudate nucleus is an important part of the brain's learning and memory system.-Anatomy:...
and putamenPutamenThe putamen is a round structure located at the base of the forebrain . The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that comprises the basal ganglia. Through various pathways, the putamen is connected to the substantia nigra and globus pallidus...
. The pathway is involved in the basal ganglia motor loop. - Tuberoinfundibular pathwayTuberoinfundibular pathwayThe tuberoinfundibular pathway refers to a population of dopamine neurons in the arcuate nucleus of the mediobasal hypothalamus that project to the median eminence . It is one of the four major dopamine pathways in the brain...
runs from the hypothalamus to the pituitary gland.
This innervation explains many of the effects of activating this dopamine system. For instance, the mesolimbic pathway
Mesolimbic pathway
The mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex...
connects the VTA and nucleus accumbens
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...
; both are central to the brain reward system
Reward system
In neuroscience, the reward system is a collection of brain structures which attempts to regulate and control behavior by inducing pleasurable effects...
.
Whilst the distinction between pathways is widely used, and is regarded as a “convenient heuristic when considering the dopamine system”, it is not absolute, and there is some overlap in the projection targets of each group of neurons.
Tonic and phasic activity
The level of extracellular dopamine is modulated by two mechanisms, tonic and phasic dopamine transmission. Tonic dopamine transmission occurs when small amounts of dopamine are released independently of neuronal activity, and is regulated by the activity of other neurons and neurotransmitter reuptake. Phasic dopamine release results from the activity of the dopamine-containing cells themselves. This activity is characterized by irregular pacemakingPacemaker action potential
A pacemaker action potential is the kind of action potential that provides a reference rhythm for the network. This contrasts with pacemaker potential or current which drives rhythmic modulation of firing rate....
activity of single spikes, and rapid bursts of typically 2-6 spikes in quick succession. Concentrated bursts of activity result in a greater increase of extracellular dopamine levels than would be expected from the same number of spikes distributed over a longer period of time.
Reuptake inhibition and synaptic release
Cocaine and amphetamines inhibit the re-uptake of dopamine; however, they influence separate mechanisms of action. Cocaine is a dopamine transporterDopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...
and norepinephrine transporter
Norepinephrine transporter
The norepinephrine transporter , also known as solute carrier family 6 member 2 , is a protein that in humans is encoded by the SLC6A2 gene....
blocker that competitively inhibits dopamine uptake to increase the lifetime of dopamine and augments an overabundance of dopamine (an increase of up to 150 percent) within the parameters of the dopamine neurotransmitters. Like cocaine, amphetamines increase the concentration of dopamine in the synaptic
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
gap, but by a different mechanism. Amphetamines and methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
are similar in structure to dopamine, and so can enter the terminal bouton of the presynaptic neuron via its dopamine transporters as well as by diffusing through the neural membrane directly. By entering the presynaptic neuron, amphetamines force dopamine molecules out of their storage vesicles
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...
and expel them into the synaptic gap by making the dopamine transporters work in reverse.
Motor control
Dopamine reduces the influence of the indirect pathway while increasing the actions of the direct pathway within the basal gangliaBasal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
. Insufficient dopamine biosynthesis
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
in the dopaminergic neurons can cause Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
, a condition in which one loses the ability to execute smooth, controlled movements.
Regulating prolactin secretion
Dopamine is the primary neuroendocrine inhibitor of the secretion of prolactinProlactin
Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
from the anterior pituitary
Anterior pituitary
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
gland. Dopamine produced by neurons in the arcuate nucleus
Arcuate nucleus
The arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence...
of the hypothalamus is secreted into the hypothalamo-hypophysial blood vessels of the median eminence
Median eminence
The median eminence is part of the inferior boundary for the hypothalamus part of the human brain. A small swelling on the tuber cinereum posterior to the infundibulum - atop the pituitary stalk - the median eminence lies in the area roughly bounded on its posterolateral region by the cerebral...
, which supply the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
. The lactotrope cells that produce prolactin
Prolactin
Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
, in the absence of dopamine, secrete prolactin continuously; dopamine inhibits this secretion. Thus, in the context of regulating prolactin secretion, dopamine is occasionally called prolactin-inhibiting factor (PIF), prolactin-inhibiting hormone (PIH), or prolactostatin.
Cognition and frontal cortex
In the frontal lobeFrontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...
s, dopamine controls the flow of information from other areas of the brain. Dopamine disorders in this region of the brain can cause a decline in neurocognitive
Neurocognitive
Neurocognitive is a term used to describe cognitive functions closely linked to the function of particular areas, neural pathways, or cortical networks in the brain substrate layers of neurological matrix at the cellular molecular level...
functions, especially memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
, attention
Attention
Attention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....
, and problem-solving. Reduced dopamine concentrations in the prefrontal cortex are thought to contribute to attention deficit disorder. It has been found that D1 receptors as well as D4 receptors are responsible for the cognitive-enhancing effects of dopamine, whereas D2 receptors are more specific for motor actions.
Chemoreceptor trigger zone
Dopamine is one of the neurotransmitters implicated in the control of nauseaNausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting via interactions in the chemoreceptor trigger zone
Chemoreceptor trigger zone
The chemoreceptor trigger zone , is an area of the medulla that receives inputs from blood-borne drugs or hormones, and communicates with the vomiting center, to initiate vomiting. The CTZ is close to the area postrema on the floor of the fourth ventricle and is outside of the blood-brain barrier...
. Metoclopramide
Metoclopramide
Metoclopramide is an antiemetic and gastroprokinetic agent. It is commonly used to treat nausea and vomiting, to facilitate gastric emptying in people with gastroparesis, and as a treatment for the gastric stasis often associated with migraine headaches.-Medical uses:Metoclopramide is commonly...
is a D2-receptor antagonist that functions as a prokinetic/antiemetic
Antiemetic
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer....
.
Effects of drugs that reduce dopamine activity
In humans, drugs that reduce dopamine activity (neuroleptics, e.g. antipsychoticAntipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
s) have been shown to impair concentration, reduce motivation, cause anhedonia
Anhedonia
In psychology and psychiatry, anhedonia is defined as the inability to experience pleasure from activities usually found enjoyable, e.g. hobbies, exercise, social interaction or sexual activity....
(inability to experience pleasure), and long-term use has been associated with tardive dyskinesia
Tardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
, an irreversible movement disorder. Antipsychotics have significant effects on gonadal hormones including significantly lower levels of estradiol and progesterone in women whereas men display significantly lower levels of testosterone and DHEA when undergoing antipsychotic drug treatment compared to controls. Antipsychotics are known to cause hyperprolactinaemia
Hyperprolactinaemia
Hyperprolactinaemia or hyperprolactinemia is the presence of abnormally-high levels of prolactin in the blood. Normal levels are less than 500 mIU/L for women, and less than 450 mIU/L for men....
leading to amenorrhea, cessation of normal cyclic ovarian function, loss of libido, occasional hirsutism
Hirsutism
Hirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...
, false positive pregnancy tests, and long-term risk of osteoporosis in women. The effects of hyperprolactinemia in men are gynaecomastia, lactation
Lactation
Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, however it predates mammals. In humans the process of feeding milk is called breastfeeding or nursing...
, impotence, loss of libido
Libido
Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...
, and hypospermatogenesis
Spermatogenesis
Spermatogenesis is the process by which male primary germ cells undergo division, and produce a number of cells termed spermatogonia, from which the primary spermatocytes are derived. Each primary spermatocyte divides into two secondary spermatocytes, and each secondary spermatocyte into two...
. Furthermore, antipsychotic drugs are associated with weight gain
Weight gain
Weight gain is an increase in body weight. This can be either an increase in muscle mass, fat deposits, or excess fluids such as water.-Description:...
, diabetes, drooling
Drooling
Drooling is when saliva flows outside the mouth...
, dysphoria
Dysphoria
Dysphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of depression, discontent and indifference to the world around them.Mood disorders can induce dysphoria, often with a heightened risk of suicide, especially in...
(abnormal depression and discontent), fatigue, sexual dysfunction
Sexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....
, heart rhythm
Heart Rhythm
Heart Rhythm is a peer-reviewed medical journal that covers the study and management of cardiac arrhythmia. It is the official journal of the Heart Rhythm Society and the Cardiac Electrophysiology Society...
problems, stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
and heart attack.
Selective D2/D3 agonists pramipexole
Pramipexole
Pramipexole is a non-ergoline dopamine agonist indicated for treating early-stage Parkinson's disease and restless legs syndrome...
and ropinirole
Ropinirole
Ropinirole is a non-ergoline dopamine agonist. It is manufactured by GlaxoSmithKline , Cipla and Sun Pharmaceutical. It is used in the treatment of Parkinson's disease...
, used to treat restless legs syndrome
Restless legs syndrome
Restless legs syndrome or Willis-Ekbom disease is a neurological disorder characterized by an irresistible urge to move one's body to stop uncomfortable or odd sensations. It most commonly affects the legs, but can affect the arms, torso, and even phantom limbs...
(RLS), have limited anti-anhedonic properties as measured by the Snaith-Hamilton Pleasure Scale (SHAPS).
Opioid and cannabinoid transmission
OpioidOpioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
and cannabinoid transmission instead of dopamine may modulate consummatory pleasure and food palatability (liking).
This could explain why animals' "liking" of food is independent of brain dopamine concentration. Other consummatory pleasures, however, may be more associated with dopamine. One study found that both anticipatory and consummatory measures of sexual behavior (male rats) were disrupted by DA receptor antagonists.
Libido can be increased by drugs that affect dopamine, but not by drugs that affect opioid peptide
Opioid peptide
Opioid peptides are short sequences of amino acids that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Opioid peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but they all resemble opiates...
s or other neurotransmitters.
Learning, reinforcement, and reward-seeking behavior
Dopamine is commonly associated with the reward systemReward system
In neuroscience, the reward system is a collection of brain structures which attempts to regulate and control behavior by inducing pleasurable effects...
of the brain, providing feelings of enjoyment and reinforcement
Reinforcement
Reinforcement is a term in operant conditioning and behavior analysis for the process of increasing the rate or probability of a behavior in the form of a "response" by the delivery or emergence of a stimulus Reinforcement is a term in operant conditioning and behavior analysis for the process of...
to motivate a person proactively to perform certain activities. Dopamine is released (particularly in areas such as the nucleus accumbens
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...
and prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...
) by rewarding
Reward system
In neuroscience, the reward system is a collection of brain structures which attempts to regulate and control behavior by inducing pleasurable effects...
experiences such as food
Food
Food is any substance consumed to provide nutritional support for the body. It is usually of plant or animal origin, and contains essential nutrients, such as carbohydrates, fats, proteins, vitamins, or minerals...
, sex, drugs
DRUGS
Destroy Rebuild Until God Shows are an American post-hardcore band formed in 2010. They released their debut self-titled album on February 22, 2011.- Formation :...
, and neutral stimuli
Neutral stimulus
A neutral stimulus is a stimulus which initially produces no specific response other than focusing attention. In classical conditioning, when used together with an unconditioned stimulus, the neutral stimulus becomes a conditioned stimulus....
that become associated
Classical conditioning
Classical conditioning is a form of conditioning that was first demonstrated by Ivan Pavlov...
with them. Recent studies indicate that aggression
Aggression
In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause humiliation, pain, or harm. Ferguson and Beaver defined aggressive behavior as "Behavior which is intended to increase the social dominance of...
may also stimulate the release of dopamine in this way.
This theory can be discussed in terms of drugs such as cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
, nicotine
Nicotine
Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
, and amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
s, which directly or indirectly lead to an increase of dopamine in the mesolimbic reward pathway
Mesolimbic pathway
The mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex...
of the brain, and in relation to neurobiological theories of chemical addiction
Physical dependence
Physical dependence refers to a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms of withdrawal result from abrupt discontinuation or dosage reduction...
(not to be confused with psychological dependence
Substance dependence
The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...
), arguing that this dopamine pathway
Dopaminergic pathways
Dopaminergic pathways are neural pathways in the brain which transmit the neurotransmitter dopamine from one region of the brain to another.The neurons of the dopaminergic pathways have axons which run the entire length of the pathway...
is pathologically altered in addicted persons.
Dopaminergic neurons of the midbrain are the main source of dopamine in the brain. Dopamine has been shown to be involved in the control of movements, the signaling of error in prediction of reward, motivation, and cognition. Cerebral dopamine depletion is the hallmark of Parkinson's disease. Other pathological states have also been associated with dopamine dysfunction, such as schizophrenia, autism, and attention deficit hyperactivity disorder, as well as drug abuse.
Dopamine is closely associated with reward-seeking behaviors, such as approach, consumption, and addiction. Recent researches suggest that the firing of dopaminergic neurons is a motivational substance as a consequence of reward-anticipation. This hypothesis is based on the evidence that, when a reward is greater than expected, the firing of certain dopaminergic neurons increases, which consequently increases desire or motivation towards the reward. However, recent research finds that while some dopaminergic neurons react in the way expected of reward neurons, others do not and seem to respond in regard to unpredictability. This research finds the reward neurons predominate in the ventromedial region in the substantia nigra pars compacta as well as the ventral tegmental area. Neurons in these areas project mainly to the ventral striatum
Ventral striatum
The ventral striatum is generally considered that part of the striatum that is connectionally associated with limbic structures, such as the amygdala, hippocampus, midline thalamus, and certain regions of the prefrontal cortex...
and thus might transmit value-related information in regard to reward values. The nonreward neurons are predominate in the dorsolateral area of the substantia nigra pars compacta which projects to the dorsal striatum
Dorsal striatum
The dorsal striatum, corpus striatum or striated body is a compound structure consisting of the caudate nucleus, and the lentiform nucleus...
and may relate to orienting behaviour. It has been suggested that the difference between these two types of dopaminergic neurons arises from their input: reward-linked ones have input from the basal forebrain
Basal forebrain
The basal forebrain is a collection of structures located ventrally to the striatum. It is considered to be the major cholinergic output of the central nervous system . It includes a group of structures that lie near the bottom of the front of the brain, including the nucleus basalis, diagonal band...
while the nonreward-related ones from the lateral habenula.
Animal studies
Clues to dopamine's role in motivation, desire, and pleasure have come from studies performed on animals. In one such study, rats were depleted of dopamine by up to 99 percent in the nucleus accumbensNucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...
and neostriatum using 6-hydroxydopamine.
With this large reduction in dopamine, the rats would no longer eat by their own volition. The researchers then force-fed the rats food and noted whether they had the proper facial expressions indicating whether they liked or disliked it. The researchers of this study concluded that the reduction in dopamine did not reduce the rat's consummatory pleasure, only the desire to actually eat. In another study, mutant hyperdopaminergic (increased dopamine) mice show higher "wanting" but not "liking" of sweet rewards.
Salience
Dopamine may also have a role in the salienceSalience (neuroscience)
The salience of an item – be it an object, a person, a pixel, etc – is the state or quality by which it stands out relative to its neighbours...
of potentially important stimuli, such as sources of reward or of danger. This hypothesis argues that dopamine assists decision-making by influencing the priority, or level of desire, of such stimuli to the person concerned.
Dopamine's role in experiencing pleasure has been questioned by several researchers. It has been argued that dopamine is more associated with anticipatory desire and motivation (commonly referred to as "wanting") as opposed to actual consummatory pleasure (commonly referred to as "liking").
Latent inhibition and creative drive
Dopamine in the mesolimbic pathwayMesolimbic pathway
The mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex...
increases general arousal
Arousal
Arousal is a physiological and psychological state of being awake or reactive to stimuli. It involves the activation of the reticular activating system in the brain stem, the autonomic nervous system and the endocrine system, leading to increased heart rate and blood pressure and a condition of...
and goal directed behaviors and decreases latent inhibition
Latent inhibition
Latent inhibition is a technical term used in Classical conditioning. A stimulus that has not had any significance in the past takes longer to acquire meaning than a new stimulus...
; all three effects increase the creative drive of idea generation. This has led to a three-factor model of creativity
Creativity
Creativity refers to the phenomenon whereby a person creates something new that has some kind of value. What counts as "new" may be in reference to the individual creator, or to the society or domain within which the novelty occurs...
involving the frontal lobe
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...
s, the temporal lobe
Temporal lobe
The temporal lobe is a region of the cerebral cortex that is located beneath the Sylvian fissure on both cerebral hemispheres of the mammalian brain....
s, and mesolimbic dopamine.
Sociability
Sociability is also closely tied to dopamine neurotransmission. Low D2 receptor-binding is found in people with social anxietySocial anxiety
Social anxiety is anxiety about social situations, interactions with others, and being evaluated or scrutinized by other people...
. Traits common to negative schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
(social withdrawal, apathy
Apathy
Apathy is a state of indifference, or the suppression of emotions such as concern, excitement, motivation and passion. An apathetic individual has an absence of interest in or concern about emotional, social, spiritual, philosophical or physical life.They may lack a sense of purpose or meaning in...
, anhedonia
Anhedonia
In psychology and psychiatry, anhedonia is defined as the inability to experience pleasure from activities usually found enjoyable, e.g. hobbies, exercise, social interaction or sexual activity....
) are thought to be related to a hypodopaminergic state in certain areas of the brain. In instances of bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
, manic
Manic
Manić is a suburban settlement of Belgrade, the capital of Serbia. It is located in the municipality of Barajevo.Manić developed on the eastern slopes of the Kosmaj mountain...
subjects can become hypersocial, as well as hypersexual. This is credited to an increase in dopamine, because mania can be reduced by dopamine-blocking antipsychotics.
Processing of pain
Dopamine has been demonstrated to play a role in painPain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
processing in multiple levels of the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
including the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
, periaqueductal gray
Periaqueductal gray
Periaqueductal gray is the gray matter located around the cerebral aqueduct within the tegmentum of the midbrain. It plays a role in the descending modulation of pain and in defensive behaviour...
(PAG), thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
, basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
, insular cortex
Insular cortex
In each hemisphere of the mammalian brain the insular cortex is a portion of the cerebral cortex folded deep within the lateral sulcus between the temporal lobe and the frontal lobe. The cortical area overlying it towards the lateral surface of the brain is the operculum...
, and cingulate cortex
Cingulate cortex
The cingulate cortex is a part of the brain situated in the medial aspect of the cortex. It includes the cortex of the cingulate gyrus, which lies immediately above the corpus callosum, and the continuation of this in the cingulate sulcus...
. Accordingly, decreased levels of dopamine have been associated with painful symptoms that frequently occur in Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
. Abnormalities in dopaminergic neurotransmission have also been demonstrated in painful clinical conditions, including burning mouth syndrome, fibromyalgia
Fibromyalgia
Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...
, and restless legs syndrome
Restless legs syndrome
Restless legs syndrome or Willis-Ekbom disease is a neurological disorder characterized by an irresistible urge to move one's body to stop uncomfortable or odd sensations. It most commonly affects the legs, but can affect the arms, torso, and even phantom limbs...
. In general, the analgesic capacity of dopamine occurs as a result of dopamine D2 receptor activation; however, exceptions to this exist in the PAG, in which dopamine D1 receptor activation attenuates pain presumably via activation of neurons involved in descending inhibition. In addition, D1 receptor activation in the insular cortex appears to attenuate subsequent pain-related behavior.
Behavior disorders
Deficient dopamine neurotransmission is implicated in attention-deficit hyperactivity disorderAttention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...
, and stimulant medications used to successfully treat the disorder increase dopamine neurotransmission, leading to decreased symptoms. Consistent with this hypothesis, dopaminergic pathways have a role in inhibitory action control and the inhibition of the tendency to make unwanted actions.
The long term use of levodopa
Levodopa
L-DOPA is a chemical that is made and used as part of the normal biology of some animals and plants. Some animals including humans make it via biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine , and epinephrine collectively...
in Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
has been linked to dopamine dysregulation syndrome
Dopamine dysregulation syndrome
Dopamine dysregulation syndrome , sometimes known as hedonistic homeostatic dysregulation in Parkinson's disease, is a dysfunction of the reward system in subjects with Parkinson's disease due to a long exposure to dopamine replacement therapy...
.
Dopaminergic mind hypothesis
The dopaminergic mind hypothesis seeks to explain the differences between modern humans and their hominid relatives by focusing on changes in dopamine. It theorizes that increased levels of dopamine were part of a general physiological adaptation due to an increased consumption of meat around two million years ago in Homo habilisHomo habilis
Homo habilis is a species of the genus Homo, which lived from approximately at the beginning of the Pleistocene period. The discovery and description of this species is credited to both Mary and Louis Leakey, who found fossils in Tanzania, East Africa, between 1962 and 1964. Homo habilis Homo...
, and later enhanced by changes in diet and other environmental and social factors beginning approximately 80,000 years ago. Under this theory, the "high-dopamine" personality is characterized by high intelligence, a sense of personal destiny, a religious/cosmic preoccupation, an obsession with achieving goals and conquests, an emotional detachment that in many cases leads to ruthlessness, and a risk-taking mentality. High levels of dopamine are proposed to underlie increased psychological disorders in industrialized societies. According to this hypothesis, a "dopaminergic society" is an extremely goal-oriented, fast-paced, and even manic society, "given that dopamine is known to increase activity levels, speed up our internal clocks and create a preference for novel over unchanging environments." In the same way that high-dopamine individuals lack empathy and exhibit a more masculine behavioral style, dopaminergic societies are "typified by more conquest, competition, and aggression than nurturance and communality." Although behavioral evidence and some indirect anatomical evidence (e.g., enlargement of the dopamine-rich striatum in humans) support a dopaminergic expansion in humans, there is still no direct evidence that dopamine levels are markedly higher in humans relative to other apes. However, recent discoveries about the sea-side settlements of early man may provide evidence of dietary changes consistent with this hypothesis.
Links to psychosis
Abnormally high dopaminergic transmission has been linked to psychosisPsychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
and schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
. Increased dopaminergic functional activity, specifically in the mesolimbic pathway
Mesolimbic pathway
The mesolimbic pathway is one of the dopaminergic pathways in the brain. The pathway begins in the ventral tegmental area of the midbrain and connects to the limbic system via the nucleus accumbens, the amygdala, and the hippocampus as well as to the medial prefrontal cortex...
, is found in schizophrenic individuals. However, decreased activity in another dopaminergic pathway, the mesocortical pathway
Mesocortical pathway
The mesocortical pathway is a neural pathway that connects the ventral tegmentum to the cerebral cortex, particularly the frontal lobes. It is one of the four major dopamine pathways in the brain...
, may also be involved. The two pathways are thought to be responsible for differing sets of symptoms seen in schizophrenia. Antipsychotic
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
s act largely as dopamine antagonists, inhibiting dopamine at the receptor
Dopamine receptor
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....
level, and thereby blocking the effects of the neurochemical in a dose-dependant manner. The older, so-called typical antipsychotics most commonly act on D2 receptors, while the atypical drugs
Atypical antipsychotic
The atypical antipsychotics are a group of antipsychotic tranquilizing drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA approved for use in the treatment of schizophrenia...
also act on D1, D3 and D4 receptors. The finding that drugs such as amphetamines, methamphetamine and cocaine, which can increase dopamine levels by more than tenfold, can temporarily cause psychosis, provides further evidence for this link.
Therapeutic use
Levodopa is a dopamine precursor used in various forms to treat Parkinson's diseaseParkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
and dopa-responsive dystonia
Dystonia
Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...
. It is typically co-administered with an inhibitor of peripheral decarboxylation (DDC, dopa decarboxylase), such as carbidopa
Carbidopa
Carbidopa is a drug given to people with Parkinson's disease in order to inhibit peripheral metabolism of levodopa.- Pharmacology :...
or benserazide
Benserazide
Benserazide is a peripherally-acting aromatic L-amino acid decarboxylase or DOPA decarboxylase inhibitor, which is unable to cross the blood-brain barrier.- Indications :...
. Inhibitors of alternative metabolic route for dopamine by catechol-O-methyl transferase
Catechol-O-methyl transferase
Catechol-O-methyltransferase is one of several enzymes that degrade catecholamines such as dopamine, epinephrine, and norepinephrine. In humans, catechol-O-methyltransferase protein is encoded by the COMT gene...
are also used. These include entacapone
Entacapone
Entacapone is a drug that functions as a catechol-O-methyl transferase inhibitor. It is used in the treatment of Parkinson's disease....
and tolcapone
Tolcapone
Tolcapone is a drug that inhibits the enzyme catechol-O-methyl transferase . - Uses :Tolcapone is used in the treatment of Parkinson's disease as an adjunct to levodopa/carbidopa medication.- Chemistry :...
.
Renal and cardiovascular
Dopamine (brand name Intropin) also has effects when administered through an IVIntravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
line outside the central nervous system. The effects in this form are dose dependent.
- Dopamine induces natriuresisNatriuresisNatriuresis is the process of excretion of sodium in the urine via action of the kidneys. Natriuresis is promoted by Brain and Atrial natriuretic peptides, and it is inhibited by chemicals such as aldosterone...
(sodium loss) in the kidneyKidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s, and has a diuretic effect, potentially increasing urine output from 5 ml/kg/hr to 10 ml/kg/hr. Dosages from 2 to 5 μg/kg/min are considered the "renal dose". At this low dosage, dopamine binds D1Dopamine receptor D1Dopamine receptor D1, also known as DRD1, is a protein that in humans is encoded by the DRD1 gene.- Function :This gene encodes the D1 subtype of the dopamine receptor. The D1 subtype is the most abundant dopamine receptor in the central nervous system. This G-protein-coupled receptor stimulates...
receptors, dilating blood vessels, increasing blood flow to renalRenal arteryThe renal arteries normally arise off the side of the abdominal aorta, immediately below the superior mesenteric artery, and supply the kidneys with blood. Each is directed across the crus of the diaphragm, so as to form nearly a right angle with the aorta....
, mesenteric, and coronary arteries, thus increasing overall renal perfusion.
- Intermediate dosages from 5 to 10 μg/kg/min, known as the "cardiac dose", additionally have a positive inotropic and chronotropicChronotropicChronotropic effects are those that change the heart rate.Chronotropic drugs may change the heart rate by affecting the nerves controlling the heart, or by changing the rhythm produced by the sinoatrial node...
effect through increased β1 receptorBeta-1 adrenergic receptorThe beta-1 adrenergic receptor , also known as ADRB1, is a beta-adrenergic receptor, and also denotes the human gene encoding it...
activation. Dopamine is used in patients with shock or heart failure to increase cardiac outputCardiac outputCardiac output is the volume of blood being pumped by the heart, in particular by a left or right ventricle in the time interval of one minute. CO may be measured in many ways, for example dm3/min...
and blood pressureBlood pressureBlood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
. Dopamine begins to affect the heart at lower doses, from about 3 μg/kg/min IV.
- High doses from 10 to 20 μg/kg/min are the "pressor dose". This dose causes vasoconstriction, increases systemic vascular resistance, and increases blood pressure through α1 receptor activation, but can cause the vessels in the kidneys to constrict to the point that urine output is reduced.
Immunoregulatory
Dopamine acts upon receptors present on immune cells, with all subtypes of dopamine receptors found on leukocytes. There is low expression of receptors on T lymphocytes and monocyteMonocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
s, moderate expression on neutrophils and eosinophils, and high expression on B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s and natural killer cell
Natural killer cell
Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...
s. The sympathetic innervation
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
of lymphoid tissues is dopaminergic, and increases during stress. Dopamine can also affect immune cells in the spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
, bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, and blood circulation. In addition, dopamine can be synthesized and released by the immune cells themselves.
The effects of dopamine on immune cells depend upon their physiological state. While dopamine activates resting T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s, it inhibits them when they are activated. Disorders such as schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
and Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
, in which there are changes in brain dopamine receptors and dopamine signaling pathways, are also associated with altered immune functioning.
Fruit browning
Polyphenol oxidasePolyphenol oxidase
Polyphenol oxidase is a tetramer which contains four atoms of copper per molecule, and binding sites for two aromatic compounds and oxygen...
s (PPOs) are a family of enzymes responsible for the browning of fresh fruits and vegetables when they are cut or bruised. These enzymes use molecular oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
(O2) to oxidise
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....
various 1,2-diphenols
Benzenediol
Benzenediols or dihydroxybenzenes are organic chemical compounds in which two hydroxyl groups are substituted onto a benzene ring. These aromatic compounds are classed as phenols, and more specifically as polyphenols...
to their corresponding quinone
Quinone
A quinone is a class of organic compounds that are formally "derived from aromatic compounds [such as benzene or naphthalene] by conversion of an even number of –CH= groups into –C– groups with any necessary rearrangement of double bonds," resulting in "a fully conjugated cyclic dione structure."...
s. The natural substrate for PPOs in banana
Banana
Banana is the common name for herbaceous plants of the genus Musa and for the fruit they produce. Bananas come in a variety of sizes and colors when ripe, including yellow, purple, and red....
s is dopamine. The product of their oxidation, dopamine quinone, spontaneously oxidises to other quinones. The quinones then polymerise and condense with amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s and protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s to form brown pigments
Biological pigment
Biological pigments, also known simply as pigments or biochromes are substances produced by living organisms that have a color resulting from selective color absorption. Biological pigments include plant pigments and flower pigments...
known as melanin
Melanin
Melanin is a pigment that is ubiquitous in nature, being found in most organisms . In animals melanin pigments are derivatives of the amino acid tyrosine. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and their reduced forms...
s. The quinones and melanins derived from dopamine may help protect damaged fruit and vegetables against growth of bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
and fungi.
See also
- AddictionSubstance use disorderSubstance use disorders include substance abuse and substance dependence. In DSM-IV, the conditions are formally diagnosed as one or the other, but it has been proposed that DSM-5 combine the two into a single condition called "Substance-use disorder"....
- AmphetamineAmphetamineAmphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
- AntipsychoticAntipsychoticAn antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
- CatecholamineCatecholamineCatecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...
- Catechol-O-methyl transferaseCatechol-O-methyl transferaseCatechol-O-methyltransferase is one of several enzymes that degrade catecholamines such as dopamine, epinephrine, and norepinephrine. In humans, catechol-O-methyltransferase protein is encoded by the COMT gene...
- Classical conditioningClassical conditioningClassical conditioning is a form of conditioning that was first demonstrated by Ivan Pavlov...
- Operant conditioningOperant conditioningOperant conditioning is a form of psychological learning during which an individual modifies the occurrence and form of its own behavior due to the association of the behavior with a stimulus...
- CocaineCocaineCocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
- DepressionDepression (mood)Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
- Dopamine hypothesis of schizophreniaDopamine hypothesis of schizophreniaThe dopamine hypothesis of schizophrenia or the dopamine hypothesis of psychosis is a model attributing symptoms of schizophrenia to a disturbed and hyperactive dopaminergic signal transduction. The model draws evidence from the observation that a large number of antipsychotics have...
- Dopamine reuptake inhibitorDopamine reuptake inhibitorA dopamine reuptake inhibitor is a type of drug that acts as a reuptake inhibitor for the neurotransmitter dopamine by blocking the action of the dopamine transporter...
s - DopaminergicDopaminergicDopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
- MethylphenidateMethylphenidateMethylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
- NeurotransmitterNeurotransmitterNeurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
- Parkinson's diseaseParkinson's diseaseParkinson's disease is a degenerative disorder of the central nervous system...
- ProlactinomaProlactinomaA prolactinoma is a benign tumor of the pituitary gland that produces a hormone called prolactin. It is the most common type of pituitary tumor...
- SchizophreniaSchizophreniaSchizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
- SelegilineSelegilineSelegiline is a drug used for the treatment of early-stage Parkinson's disease, depression and senile dementia. In normal clinical doses it is a selective irreversible MAO-B inhibitor, however in larger doses it loses its specificity and also inhibits MAO-A...
- SerotoninSerotoninSerotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...