How to increase Dopamine with Scio Tech and Natural

Dopamine and SCIO technology
Dopamine is a neurotransmitter. It is a chemical messenger that helps in the transmission of
signals in the brain and other vital areas. Dopamine is found in humans as well as animals,
including both vertebrates and invertebrates.
Dopamine is commonly known as a chemical produced by the brain that relates to the sensation
of pleasure. Dopamine regulates virtually all bodily functions, including eye movement,
heartbeat and breathing. Various types of dopamine (there are several) must exist in carefully
regulated amounts in order for these functions to be properly controlled.
With too little dopamine movement becomes difficult. Parkinson's disease is one result of low
levels of dopamine. Too much dopamine results in hyperactivity and an inability to remain still.
The most extreme form of this is tardive dyskinesia.
The Film Awakenings
A story of Dopamine
Deficiency followed by
Excess
Accuracy of The 1990 Film Awakenings
Andrew Clapper
University of North Carolina at Chapel Hill
Normally, films that are based upon actual events take a great deal of liberty in
changing the details of the events that they depict. Awakenings appears to be an exception
to this trend. Although the names of people involved are changed, and the methodology of
treatment for a disease is different, the movie seems to depict a particular disease and the
drug used to treat it very accurately. The film is based upon the book with the same name,
which was written by Dr. Oliver Sacks. Dr. Sacks recommended that his name be changed,
and so we follow a fictional Dr. Sayer through the summer of 1969 in the Bronx, New
York. Dr. Sayer uses a new drug to try to treat some patients that appear to be catatonic,
and for a time he is successful. However, patients who are treated with the drug develop a
tolerance for it, and soon his patients return to their former state. The movie appears to
give the audience a close approximation of the symptoms of the disease, as well as the side
effects of the drug that was used to treat it.
The film Awakenings begins with a depiction of one of the main characters as a
child. The child is named Leonard Lowe, and he becomes one of many victims of an
epidemic of encephalitis lethargica that spread worldwide from 1917 to 1928. As his
sickness progresses, he is no longer able to spend time with his friends, for fear of
spreading the disease and perhaps to prevent him from being helpless should he have an
attack. The film then skips forward to 1969, where we see a Dr. Sayer apply for a job at a
hospital in the Bronx. Although Dr. Sayer's experience is all in research with non-human
subjects, the hospital is understaffed and hires him. Dr. Sayer is determined to investigate
ways to improve the quality of life for his patients, despite the skepticism of his
peers. Also, instead of conducting business in a routine manner as the other doctors at the
hospital seem to do, Sayer dedicates himself to investigation and testing. His investigation
of multiple patients with catatonic conditions leads to the discovery that many of the
patients with catatonic behavior suffered from encephalitis lethargica at some point in the
past. To learn more about them, Sayer consults another doctor that treated many victims of
the encephalitis lethargica. Many of the patients that survived the outbreak seemed to
recover for a time, but after a number of years they gradually became catatonic. A short
time later, the fact that the catatonic behavior of the encephalitis patients is similar to that
of Parkinson's patients, so he investigates the latest advances in Parkinson's treatments. At
a conference on Parkinson's treatments, Sayer first learns about Levodopa (L Dopa). Sayer
proposes that L Dopa be tried as a treatment for one of his catatonic patients, although his
superiors doubt he will be successful. He selects Leonard Lowe for the first series of L
Dopa treatments. After a time, Leonard awakens from his catatonic state and his mother
sees him fully conscious for the first time since he was a child. Sayer then lobbies the
patrons of the hospital for additional funding to expand the L Dopa treatments to the rest of
the encephalitic patients, and when they see film footage of Leonard before and after his
treatments, they enthusiastically begin writing checks. Virtually all of the patients
experience what appears to be a full recovery, and for a time they are able to lead the
normal life that is often taken for granted. Unfortunately, it is not long before Leonard
begins to experience side effects of L Dopa administration. He begins to experience
convulsions, paranoia, and psychotic behavior. His body also begins to build a tolerance
for it, so that his Parkinsonian symptoms begin to return. Although Dr. Sayer vows not to
give up, Leonard eventually returns to his previous catatonic state. After a time, the rest of
Sayer's patients experience the same course of events. The film ends with a speech given
by Sayer, who reflects on the lessons that his patients taught him over the course of the
previous summer.
In order to understand whether the film Awakenings is accurate, it is important to
convey basic information about encephalitis lethargica. From 1917 to 1928, encephalitis
lethargica was epidemic worldwide. It is estimated that over five million people died from
causes related to the disease. The leading theory on the cause of encephalitis lethargica is
that the disease results from a strong immune system reaction to an infection by bacterium
related to streptococcus. Researchers have found that antibodies have bound themselves to
neurons in the basal ganglia and midbrain in encephalitis lethargica (EL) patients. The
symptoms of EL often begin with a high fever, headache, and sore throat. Other symptoms
follow, including tremors, muscle pains, a slowing of physical and mental response, and
drowsiness. At times, a person infected with EL may see behavioral and personality
changes, and sometimes they can become psychotic. Unfortunately, there is little to be
done in the way of treatment for those suffering form encephalitis besides attempting to
stabilize the patient. The patient is kept hydrated with intravenous fluids and watched
carefully for signs of brain swelling. If needed, they are treated with anticonvulsants to
control seizures. If the disease becomes progressive, brain damage similar to that caused
by Parkinson's disease can occur. Because of Dr. Oliver Sacks' work, L Dopa is considered
a possible treatment for those with progressive EL, but unfortunately the periods of
improved quality of life are always short lived.
An understanding of the drug L Dopa is also important to ascertaining the accuracy
of Awakenings. In the 1950s, Arvid Carlsson showed that L Dopa reduced Parkinsonian
symptoms in animals. Parkinson's patients tend to show degeneration of the substantia
nigra. Normally, dopamine is released from most neurons in the substantia nigra, but
Parkinson's patients have little dopamine present there. L Dopa, which can be metabolized
into dopamine, is able to be administered as a drug because it is able to cross the blood
brain barrier. Dopamine, however, can not do so. It follows that L Dopa helps return the
dopamine levels in the substantia nigra to normal levels, and thus help the brain achieve a
more normal state of functioning (Pinel, 2007). Unfortunately, the human body develops a
tolerance of L Dopa, making its effectiveness temporary. Also, L Dopa has been
associated with a number of side effects. Some side effects that correspond with events in
Awakenings include confusion, extreme emotional states, excessive libido, fragmented
sleep, working memory improvement, and a condition similar to amphetamine psychosis.
Awakenings appears to be extremely accurate as far as EL and L Dopa are
concerned. The actors that portray EL patients with progressive states of the disease do an
excellent job of simulating what is similar to catatonic behavior. In particular, Robert
DeNiro as Leonard Lowe seems to portray the progression from awakening to L Dopa side
effects to return to the progressive EL state well. When he is first given L Dopa in the film,
he shows a gradual increase in physical and cognitive ability to what appears to be a
normal state. Later, his behavior is consistent with the side affects associated with L
Dopa. He shows an extreme emotional state and fragmented sleep when he calls Dr. Sayer
in the middle of the night and tells him that they need to tell people not to take life for
granted. Also, the film shows what may be excessive libido when Leonard shows great
interest in the women he sees when he visits the city with Sayer. Leonard also has what
appears to be a psychotic break, and he becomes paranoid and asks other patients at the
hospital to protect him. Psychotic breaks similar to those caused by amphetamines are
another known side effect of L Dopa.
Besides the fact that cars, a bus, and a jet appear in the film that were not yet being
used in 1969, there exist a few more inaccuracies. Rather than starting L Dopa treatment
with one patient and then expanding to all of the EL patients as depicted in the film, Oliver
Sacks actually began his study as a double blind procedure with a placebo group and a
treatment group. He also originally intended to conduct the study for 90 days. Once he
saw that fifty percent of his patients were showing improvement, Sacks went ahead and
began giving all of the patients L Dopa and dropped the 90 day limit on the study. Sacks'
decision to do so is a good example a particular bioethics issue. At times, experimental
drugs do not appear to be effective or cost efficient enough to continue to be used under
normal circumstances, but doctors will continue to prescribe them in order to maximize the
quality of life for their patients. Instead of going from half of the patients in a double blind
study to all of them, the film depicts Dr. Sayer going from one patient to all of his
patients. This difference in methodology appears to be the only major difference between
the events and depictions in the film and the events that the book and film are based upon
(Sacks, 1983).
Awakenings is close resemblance of the actual events that took place in
a Bronx hospital during the summer of 1969. A doctor there did treat a group of EL
patients with L Dopa, with astonishing but short lived success. The actors in the movie
simulated EL and L Dopa side effects well. Robin Williams did a good job imitating the
personality and mannerisms of Oliver Sacks as the renamed Dr. Sayer. Even though Dr.
Sayer uses methodology different than what was originally used by Sacks, overall the film
does serve as an effective educational tool for EL and L Dopa. The praise and award
nominations it received are well deserved.
References
Lasker, L. & Marshall, P. (1990). Awakenings. United States of America: Columbia
Tristar Home Video.
Pinel, J. (2007). Basics of Biopsychology. Allyn and Bacon, Boston, MA, 444 - 477.
Sacks, O. (1983). The origin of “Awakenings.” British Medical Journal, 287, 1968–1969.
Dopamine history
Dopamine was first synthesized in 1910 by George Barger and James Ewens at Wellcome
Laboratories in London, England.
In 1958, Arvid Carlsson and Nils-Åke Hillarp, at the Laboratory for Chemical Pharmacology
of the National Heart Institute of Sweden, discovered the function of dopamine as a
neurotransmitter. Arvid Carlsson was awarded the 2000 Nobel Prize in Physiology or
Medicine for showing that dopamine is not just a precursor of norepinephrine
and epinephrine but a neurotransmitter, as well.
Dopamine production
Dopamine is produced in several areas of the brain, including the substantia nigra and the
ventral tegmental area. It is a neurohormone that is released by the hypothalamus. Its
action is as a hormone that is an inhibitor or prolactin release from the anterior lobe of the
pituitary.
Dopamine Deficiency Related Symptoms and Conditions
With a dopamine deficiency, the early warning signs of deteriorating health are related to
loss of energy: physically you experience fatigue, and mentally you're sluggish. These
effects can show up in your body in a variety of ways and can affect any of the four major
domains of brain function.
A dopamine deficiency can cause any of these
symptoms:
Physical Issues:
Anemia Excessive sleep Narcolepsy
Balance problems Food cravings Nicotine cravings
Blood sugar instability Head and facial tremor Obesity
Bone density loss High Blood Pressure Parkinson’s disease
Carbohydrate binges Hyperglycemia Slow or poor metabolism
Constipation Inability to gain or lose weight Slow or rigid movements
Decreased desire for food Joint pain Substance abuse
Decreased physical strength and activity Kidney problems Sugar or junk food
cravings
Diabetes Light-headedness Tremors
Diarrhea Low sex drive Thyroid disorders
Difficulty achieving orgasm Movement disorders Trouble swallowing
Digestion problems
Personality Issues
Aggression Hedonistic behavior
Anger Inability to handle stress
Carelessness Isolating oneself from others
Depression Mood swings
Fear of being observed Procrastination
Guilt or feelings of worthlessness/ Self-destructive thoughts of hopelessness
Memory Issues:
Distractibility Lack of working memory
Failure to listen and follow instructions Poor abstract thinking
Forgetfulness Slow processing speed
Attention Issues:
Attention deficit disorder Hyperactivity
Decreased alertness Impulsive behavior
Failure to finish tasks Poor concentration
Obviously, no one person will have all of the listed symptoms of dopamine deficiency at
once. Yet all of these symptoms are treated every day by thousands of doctors, most of
whom overlook or may be unaware of the fact that they are caused by a dopamine
deficiency.
Dopamine Deficiency
Deficiency of dopamine is known to be responsible for Parkinson’s disease. Patients
suffering from this condition have problems with the movement and speech. This chronic
and progressive disease causes tremor, muscle strictness, slow movements and sometimes
even complete loss of movement. Speech problems occur in later stages of the disease and
are associated with the impaired memory and learning skills.
Patients diagnosed with the lack of DA often experience sleeping problems. In some cases,
lack of dopamine may cause excess sleep.
Dopamine deficiency might be characterized by the development of addiction to various
stimulants, coffee being one of the relatively harmless ones.
People diagnosed with lack of dopamine are often overweight, with low blood pressure
(hypotension) and dehydration. Hypotension may occur in the morning, when the patient
tries to get up from the bed and leads to dizziness. Another symptom connected to the
dopamine deficiency is low blood sugar level.
Many of the patients with lack of dopamine experience sexual problems (impotence, low
libido), depression, suicidal ideas, motivation problems and incapacity to feel the pleasure in
anything.
Neurotransmitters with discrete localization within the brain. A) The chemical structure of
the monoamine neurotransmitter dopamine and a schematic drawing of the localization of
dopamine-containing neurons in the human and rat brain and the sites where dopamine-
containing axons are found. B) The chemical structure of the monoamine
neurotransmitter serotonin and similar brain map showing locations of serotonin-containing
cells and their axons.
Dopamine receptors
Dopamine acts on receptors that are specific for it. Five subtypes of mammalian dopamine
receptors are grouped into two classes.


D1-like receptor class – This comprises of D1 and D5 receptor subtypes
D2-like receptor class – This comprises of D2, D3, and D4 receptor subtypes
These receptors have similar signalling properties. They however have different signal
transduction pathways that determine their subtypes and classes.
All of the dopamine receptors are G protein-coupled receptors (GPCRs), who’s signalling is
primarily mediated by interaction with and activation of GTP-binding proteins (G proteins).
Members of this superfamily are also called 7-transmembrane receptors because they
traverse the cell membrane seven times. They are also called serpentine receptors because
of the snake like manner in which they wind back and forth across the membrane.
Actions of dopamine
Dopamine is also used as medication. It acts on the sympathetic nervous system.
Application of dopamine leads to increased heart rate and blood pressure.
Dopamine cannot cross the blood-brain barrier, so dopamine given as a drug does not
directly affect the central nervous system.
Dopamine is needed in some brain diseases as well. This includes diseases such
as Parkinson's disease and dopa-responsive dystonia. For these patients levodopa is used.
This is a precursor of dopamine. It can cross the blood-brain barrier.
How to Increase Dopamine
Edited by Permasofty, BR, Dancing Fish, Parma and 6 others
The dopamine naturally produced by your brain makes you feel good. You get a rush of
dopamine in response to pleasurable activities like food or sex.[1] On the other hand,
without enough dopamine, you may feel sluggish, depressed and uninterested in life. Try
some different methods to boost your dopamine levels if you're feeling a little low.
EditSteps
Method 1: Increase Dopamine Through Diet, Exercise and Adequate Sleep1
Eat foods rich in tyrosine. Almonds, avocados, bananas, low-fat dairy, lima beans,
sesame seeds and pumpkin seeds may all help your body to produce more dopamine.
Increase your intake of antioxidants. Dopamine is easy to oxidize, and antioxidants
may reduce free radical damage to the brain cells that produce dopamine. Many fruits and
vegetables are rich in antioxidants, including:
o
Beta-carotene and carotenoids: Greens, orange vegetables and fruits, asparagus,
broccoli, beets
o Vitamin C: Peppers, oranges, strawberries, cauliflower, Brussels sprouts
o
Vitamin E: Nuts and sunflower seeds, greens, broccoli, carrots[2]
o
Avoid food that inhibits brain function. Such foods may include refined packaged
foods, refined white flour, cholesterol, caffeine, and saturated fats. [3]
Exercise regularly. Exercise increases blood calcium, which stimulates dopamine
production and uptake in your brain. Try 30 to 60 minutes of walking, swimming or
jogging to jump-start your dopamine
Get plenty of sleep. Your brain uses very little dopamine while you sleep, which helps
you to build up your supply naturally for the next day. Get at least 8 hours of sleep per
night.
Method 2: Increase Dopamine By Taking Supplements or Medication
Try a supplement. Some physicians recommend Vitamin B6 supplements and LPhenylalanine to elevate dopamine in the brain. You can grab either of these at your local
drugstore.[4]
Dopamine link to psychiatric
and neurological disorders
Published on October 23, 2005 at 8:30 PM ·
A gene that regulates dopamine levels in the brain is involved in the
development of schizophrenia in children at high risk for the disorder,
say researchers at the Stanford University School of Medicine, Lucile
Packard Children's Hospital and the University of Geneva.
The finding adds to mounting evidence of dopamine's link to psychiatric and neurological
disorders. It may also allow physicians to pinpoint a subset of these children for treatment
before symptoms start.
"The hope is that we will one day be able to identify the highest-risk groups and intervene
early to prevent a lifetime of problems and suffering," said Allan L. Reiss, MD. "As we gain a
much better understanding of these disorders, we can design treatments that are much
more specific and effective."
Reiss is the Robbins Professor of Psychiatry and Behavioral Sciences at Stanford and
director of the school's Center for Interdisciplinary Brain Sciences Research. He is also a
child and adolescent psychiatrist at Packard Children's Hospital at Stanford. The research,
which will be published online Oct. 23, will appear in print in the November issue of Nature
Neuroscience.
Dopamine levels have been implicated in many neurological conditions, includingParkinson's
disease and psychosis. Data from this and other studies suggest a kind of Goldilocks effect
for this important chemical messenger: too little or too much can dramatically interfere with
normal cognition, behavior and motor skills. Nudging these levels back into the "just-right"
range may help treat or cure some conditions.
Schizophrenia is a brain disease that affects about 1 percent of people in this country and
can manifest itself through agitation, catatonia and psychosis. Although the disorder
sometimes runs in families, it can also occur spontaneously. Scientists have suspected for
many years that dopamine was involved, due in part to the success of older psychiatric
drugs that function by interacting with dopamine receptors in the brain. But the root cause
of schizophrenia has remained elusive.
Reiss and the study's first author Doron Gothelf, MD, a child psychiatrist and postdoctoral
scholar at Stanford, studied 24 children with a small deletion in one copy
of chromosome 22. About 30 percent of children with this deletion, which occurs in about
one in 4,000 births, will develop schizophrenia or a related psychotic disorder. These
children also often have special facial features, cardiac defects and cleft anomalies that
often make their speech hypernasal. Although these characteristics make it possible to
identify them before psychiatric disorders develop, the disorder, called velocardiofacial
syndrome, is under-diagnosed and under-recognized in this country despite its link to
schizophrenia.
"We have strong evidence that this deletion is a major risk factor for the development of
schizophrenia or related psychotic disorders," said Reiss. "We asked, 'What is it about this
deletion that causes such an increase in risk?'"
The answer lay in the fact that one of the missing genes encodes a dopamine-degrading
protein called COMT. Natural variations in the gene generate two versions of the protein:
one with high activity, one with low.
Because most people have two copies of the gene, it doesn't usually matter which versions
of COMT they inherit; high-high, high-low and low-low all seem to provide enough COMT
activity to get the job done (though some combinations confer a mild advantage for some
cognitive tasks).
But children with the deletion have only the one copy that remains on their intact
chromosome 22. Reiss and Gothelf, who is also an assistant professor at Tel Aviv University
in Israel, surmised that a single copy of the low-activity COMT might not dispose of
enough dopamine to produce optimal brain function. They set out to determine if the clinical
course of the children with deletions who developed schizophrenia varied with the version of
the COMT protein they had.
The researchers matched the age, gender, ethnicity and IQ of the 24 children with the
deletion with 23 children with developmental disabilities of unknown causes. They then
tested their subjects' verbal IQ and cognitive abilities. None of the children in either group
had yet experienced any psychotic symptoms. They also measured the size of the children's
prefrontal cortex - an area of the brain where COMT activity is particularly important and
that is strongly associated with schizophrenia. They repeated the same tests after about five
years, when their subjects reached late adolescence or early adulthood.
As expected, about 29 percent, or seven, of the children with the deletion had developed
a psychotic disorder by the second round of testing, compared with only one child in the
control group. Of these seven, those with the low-activity version of COMT had experienced
a significantly greater drop in their verbal IQ and expressive language skills and a markedly
greater decrease in the volume of their prefrontal cortex than did their peers with the more
highly active version of COMT. The psychotic symptoms of the low-activity subset were also
significantly more severe.
In contrast, members of the control group experienced no significant differences in any of
these categories, regardless of their COMT profiles.
"What's interesting about this finding is that the disease course in the individuals with lowactivity COMT looked remarkably like idiopathic schizophrenia," said Reiss, who hopes to
use this and future data to develop a model for other causes of schizophrenia.
"Although this deletion probably causes less than 5 percent of schizophrenia cases, it's the
only well-defined genetic risk factor we have right now," said Reiss. "In the future,
researchers will likely discover multiple causes of this disorder, with complex interactions
between genetic and environmental risk factors. But COMT activity appears to be an
important contributory factor for the development of psychosis in the chromosome 22
deletion syndrome."
The researchers next plan to extend their studies to younger children, and to repeat the
above study using multiple time points to more precisely catch the ongoing development of
the disorder.
http://www.med.stanford.edu/
Dopamine
Dopamine (abbreviated as DA[1]), is a monoamine neurotransmitter and hormone, which has a number of
important physiological roles in the bodies of animals. Dopamine is a simple organic chemical in
the catecholamine family and may also be classified as a substituted phenethylamine. Its name derives from its
chemical structure, which consists of an amine group (NH2) linked to a catechol structure, called
dihydroxyphenethylamine, the decarboxylated form of dihydroxyphenylalanine(acronym DOPA).
In the brain, dopamine functions as a neurotransmitter—a chemical released by nerve cells to send signals to
other nerve cells. The human brain uses five known types of dopamine receptors, labeled D1, D2, D3, D4,
and D5. Dopamine is produced in several areas of the brain, including the substantia nigra and the ventral
tegmental area.
Dopamine plays a major role in the brain system that is responsible for reward-driven learning. Every type of
reward that has been studied increases the level of dopamine transmission in the brain, and a variety of
addictive drugs, includingstimulants such as cocaine, amphetamine, and methamphetamine, act directly on the
dopamine system.[2] Personality traits such as extraversion and reward seeking have been linked to higher
sensitivity to rewarding stimuli of the mesolimbic dopamine system.[3][4]
Several important diseases of the nervous system are associated with dysfunctions of the dopamine
system. Parkinson's disease, an age-related degenerative condition causing tremor and motor impairment, is
caused by loss of dopamine-secreting neurons in the substantia nigra. Schizophrenia has been shown to
involve elevated levels of dopamine activity in the mesolimbic pathway and decreased levels of dopamine in
the prefrontal cortex.[5][6] Attention deficit hyperactivity disorder (ADHD)[7] and restless legs
syndrome (RLS)[8][9] are also believed to be associated with decreased dopamine activity.
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 doparesponsive dystonia, L-DOPA (the precursor of dopamine) is often given because it crosses the blood–brain
barrier relatively easily.
History
Main article: History of catecholamine research
Dopamine was first synthesized in 1910 by George Barger and James Ewens at Wellcome Laboratories
[10]
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 Carlsson and Nils-Åke Hillarp at the
[11]
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.
Catecholamine biosynthesis
Dopamine is synthesized in the body from within cells (mainly by neurons and cells in the medulla of
the adrenal glands) and can be created from any one of the following three amino acids:

L-Phenylalanine

L-Tyrosine (L-4-hydroxyphenylalanine;
(PHE)
TYR)

L-DOPA (L-3,4-dihydroxyphenylalanine;
DOPA)
These amino acids are provided from natural sources such as the ingestion of various kinds of food,
with L-tyrosine being the most common of the three. Although dopamine itself is also commonly found in
many types of food, unlike the amino acids that form it, it is incapable of crossing the protective blood–
brain barrier (BBB), which severely restricts its functionality upon consumption. It must be formed from
within the walls of the BBB to properly perform its cognitive duties, though not its peripheral actions.
Dopamine itself is also used in the synthesis of the following related catecholamine neurotransmitters:

Norepinephrine (β,3,4-trihydroxyphenethylamine; Noradrenaline; NE, NA)

Epinephrine (β,3-dihydroxy-N-methylphenethylamine; Adrenaline; EPI, ADR)
This is the complete metabolic pathway:

L-Phenylalanine
→ L-Tyrosine → L-DOPA → Dopamine → Norepinephrine → Epinephrine
L-Phenylalanine
is converted into L-tyrosine by the enzyme phenylalanine hydroxylase (PAH)
with molecular oxygen (O2) and tetrahydrobiopterin (THB) as cofactors. L-Tyrosine is converted into LDOPA by the enzyme tyrosine hydroxylase (TH) with tetrahydrobiopterin (THB), O2,
2+
and ferrous iron (Fe ) as cofactors. L-DOPA is converted into dopamine by the enzyme aromatic L-amino
acid decarboxylase (AAAD; also known as DOPA decarboxylase (DDC)) with pyridoxal phosphate (PLP)
as the cofactor. The reactions are illustrated as follows:

PAH: L-Phenylalanine + THB + O2 + Fe

TH: L-Tyrosine + THB + O2 + Fe

AAAD: L-DOPA + PLP → Dopamine + PLP + CO2
2+
2+
2+
→ L-Tyrosine + DHB + H2O + Fe
2+
→ L-DOPA + DHFA + H2O + Fe
Dopamine is converted into norepinephrine by the enzyme dopamine β-hydroxylase (DBH) with O2 and Lascorbic acid as cofactors. Finally, norepinephrine is converted into epinephrine by the
enzyme phenylethanolamine N-methyltransferase (PNMT) with S-adenosyl-L-methionine (SAMe) as the
cofactor. The reactions are illustrated as follows:

DBH: Dopamine + Ascorbic Acid + O2 → Norepinephrine + DHA + H2O

PNMT: Norepinephrine + SAMe → Epinephrine + Homocysteine
It should be noted that some of the cofactors also require their own synthesis. These include:

Guanine → Guanosine → Guanosine Monophosphate (GMP) → Guanosine Diphosphate (GDP)
→ Guanosine Triphosphate (GTP)

GTP Cyclohydrolase I (GTPCH, GCH): GTP → 7,8-Dihydroneopterin Triphosphate (DHNTP)

6-Pyruvoyltetrahydropterin Synthase (PTS, PTPS): DHNTP → 6Pyruvoyltetrahydropterin (Dyspropterin)

Sepiapterin Reductase (SPR): Dyspropterin → Tetrahydrobiopterin (THB)

Folic Acid → DHFA → THFA

Pyridoxine → Pyridoxamine → Pyridoxal → PLP (requires Zn
2+
as a cofactor)

+
+
Niacin → Nicotinamide → NMN → NAD → NADH / NADP → NADPH
Deficiency in any required amino acid or cofactor will result in subsequent dopamine, norepinephrine, and
epinephrine biosynthesis impairment and deficiency as well. Conversely, supplementation with Lphenylalanine, L-tyrosine, L-DOPA, or any of the cofactors will increase their respective concentrations.
Storage, release, and reuptake
Upon synthesis, dopamine is transported from the cell cytosol into synaptic vesicles by the vesicular
monoamine transporter 2 (VMAT2). Dopamine is stored in and remains in these vesicles until an action
potential occurs and forces them to merge with the cell membrane via a process known as exocytosis,
thereby dumping dopamine into synapses.
Once in the synapse, dopamine binds to and activates postsynaptic dopamine receptors, resulting in the
signal of the presynaptic cell being propagated to the postsynaptic neuron. Dopamine also binds to
presynaptic dopamine receptors, which can either excite the presynaptic cell or inhibit it depending on
their electrical potential. Presynaptic receptors with an inhibitory potential are called autoreceptors and
inhibit neurotransmitter synthesis and release. They serve to keep dopamine levels normalized in certain
pathways when release is acutely disrupted and becomes too high or too low.
After dopamine has performed its synaptic duties, it is taken up via reuptake back into the presynaptic cell
by either the high-affinity dopamine transporter (DAT) or the low-affinity plasma membrane monoamine
transporter (PMAT). Once back in the cytosol, it is subsequently repackaged into vesicles by VMAT2.
Degradation
Dopamine degradation
Dopamine is directly broken down into inactive metabolites by two enzymes, monoamine oxidase (MAO)
and catechol-O-methyl transferase (COMT). It is equally metabolized by the two respective isoforms of
MAO,MAO-A and MAO-B.
Dopamine is metabolized by MAO into 3,4-dihydroxyphenylacetaldehyde (DOPAL). DOPAL is further
metabolized into 3,4-dihydroxyphenylacetic acid (DOPAC) by the enzyme aldehyde
dehydrogenase (ALDH). DOPAL can also be reduced to 3,4-dihydroxyphenylethanol (DOPET; also
known as hydroxytyrosol) by aldose reductase (AR) to a lesser extent. Finally, COMT reduces DOPAC
and DOPET to homovanillic acid(HVA) and 3-methoxy-4-hydroxyphenylethanol (MOPET), respectively,
which are then excreted in the urine. COMT can also directly metabolize dopamine into 3methoxytyramine (3-MT), which is then subsequently metabolized to HVA by MAO and is excreted in the
urine as well. The reactions are illustrated and summarized here:

Dopamine → DOPAL → DOPAC → HVA

Dopamine → DOPAL → DOPET → MOPET

Dopamine → 3-MT → HVA
In most areas of the brain, including the striatum and basal ganglia, dopamine is inactivated by reuptake
via the DAT, then enzymatic breakdown by MAO into DOPAC. In the prefrontal cortex, however, there are
very few DAT proteins, and dopamine is inactivated instead by reuptake via the norepinephrine
transporter (NET), presumably on neighboring norepinephrine neurons, then enzymatic breakdown by
[18]
COMT into 3-MT. The DAT pathway is roughly an order of magnitude faster than the NET pathway: in
mice, dopamine concentrations decay with a half-life of 200 milliseconds in the caudate nucleus (which
[19]
uses the DAT pathway) versus 2,000 milliseconds in the prefrontal cortex. Dopamine that is not broken
down by enzymes is repackaged into vesicles for reuse by VMAT2.
Receptors
Main article: Dopamine receptor
Dopamine binds to and activates a group of receptors called the dopamine receptors to mediate its
physiological effects in the body. The dopamine receptors are a series of five G protein-coupled
receptors (GPCRs), which consist of the D1, D2, D3, D4, and D5 receptors. As GPCRs, they work by
modulating the cyclic adenosine monophosphate (cAMP) second messenger system to produce a cellular
response. The five receptors are individually categorized into two distinctive groups based on their
varying properties and effects, the D1-like and D2-like subfamilies. The D1 and D5 receptors belong to the
D1-like subfamily. They are coupled to Gsand increase the cellular concentrations of cAMP by the
activation of the enzyme adenylate cyclase. The D2, D3, and D4 receptors belong to the D2-like subfamily.
They are coupled to Gi/Go and decrease the cellular concentrations of cAMP by inhibition of adenylate
cyclase. Ultimately, the cAMP second messenger system, through several downstream mechanisms,
works by modulating the opening of plasmalemmal ion channels that allow positively charged ions such
+
+
as Na and K to enter or exit the cytoplasm of the cell, thereby generating or inhibiting an action
potential. The receptors also couple directly to ion channels via the G-proteins. The D1-like receptors
have various effects on neuronal activity, while the D2-like receptors tend to decrease action potential
generation and are therefore usually inhibitory.
Dopamine Receptors
Family Receptor Gene
D1
Type
Mechanism
DRD1
D1-like
D5
DRD5
D2
DRD2
D2-like D3
DRD3
D4
DRD4
Gs-coupled.
Increasing intracellular levels of cAMP by activating adenylate
cyclase.
Gi/Gocoupled.
Decreasing intracellular levels of cAMP by inhibiting adenylate
cyclase.
The D1 receptor is the most widespread dopamine receptor in the central nervous system. The D 3, D4,
and D5 receptors are present in significantly lower levels than are the D 1 and D2 receptors. In fact, the
D1 receptors are approximately 100x more common than the D5 receptors. However, dopamine binds to
the D3, D4, and D5 receptors with nanomolar or submicromolar affinity constants, while its corresponding
constants for D1 and D2 receptors are in the micromolar ranges. As an example, dopamine has 20-fold
higher binding affinity for the D3 receptor in comparison to the D2 receptor, and 10-fold higher binding
affinity for the D5 receptor over the D1 receptor. Hence, overall activation of the system seem to be more
or less well-balanced.
Functions in the brain
Dopamine pathways. In the brain, dopamine plays an important role in the regulation of reward and movement. As part of
the reward pathway, dopamine is manufactured in nerve cell bodies located within the ventral tegmental area (VTA) and is
released in the nucleus accumbens and the prefrontal cortex. Its motor functions are linked to a separate pathway, with cell
bodies in the substantia nigra that manufacture and release dopamine into the striatum.
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
[20]
in lactation and sexual gratification), sleep,dreaming, 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
[21]
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
[22]
behavior. Temporal difference learningprovides a computational model describing how the prediction
[citation needed]
error of dopamine neurons is used as a teaching signal.
The reward system in insects uses octopamine, which is the presumed arthropod homolog
[23]
of norepinephrine, rather than dopamine. In insects, dopamine acts instead as a punishment signal and
[24][25]
is necessary to form aversive memories.
Anatomy
Main article: Dopaminergic pathways
Dopaminergic neurons form a neurotransmitter system which originates in substantia nigra pars
compacta, ventral tegmental area (VTA), and hypothalamus. These project axons to large areas of the
brain which are typically divided into four major pathways:

Mesocortical pathway connects the ventral tegmental area to the frontal lobe of the pre-frontal cortex.
Neurons with somas in the ventral tegmental area project axons into the pre-frontal cortex.

Mesolimbic pathway carries dopamine from the ventral tegmental area to the nucleus accumbens via
the amygdala and hippocampus. The somas of the projecting neurons are in the ventral tegmental
area.

Nigrostriatal pathway runs from the substantia nigra to the neostriatum. Somas in the substantia nigra
project axons into the caudate nucleus and putamen. The pathway is involved in the basal ganglia
motor loop.

Tuberoinfundibular pathway 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 connects the VTA and nucleus accumbens; both are central to the brain reward
[26]
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
[27]
of each group of neurons.
Cellular effects
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
[28]
reuptake. Phasic dopamine release results from the activity of the dopamine-containing cells
themselves. This activity is characterized by irregular pacemaking activity of single spikes, and rapid
[29][30]
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
[31]
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 transporter 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
[citation needed]
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.
Motor control
Dopamine reduces the influence of the indirect pathway while increasing the actions of the direct pathway
[32]
within the basal ganglia. Insufficient dopamine biosynthesis in the dopaminergic neurons can
cause Parkinson's disease, a condition in which one loses the ability to execute smooth, controlled
[32]
movements.
Regulating prolactin secretion
Dopamine is the primary neuroendocrine inhibitor of the secretion of prolactin from the anterior
[33]
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.
Cognition and frontal
In the frontal lobes, 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
[34]
cortex are thought to contribute to attention deficit disorder. It has been found that D1 receptors as well
[35]
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 nausea and vomiting via interactions
in the chemoreceptor trigger zone. Metoclopramide is a D2-receptor antagonist that functions as
a prokinetic/antiemetic.
Effects of drugs that reduce dopamine activity
In humans, drugs that reduce dopamine activity (neuroleptics, e.g. antipsychotics) have been shown to
impair concentration, reduce motivation, cause anhedonia (inability to experience pleasure), and longterm use has been associated with tardive dyskinesia, an irreversible movement
[36]
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
[37]
aregynaecomastia, 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
[38]
limited anti-anhedonic properties as measured by the Snaith-Hamilton Pleasure Scale (SHAPS).
Opioid and cannabinoid transmission
Opioid and cannabinoid transmission instead of dopamine may modulate consummatory pleasure and
[39]
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
[40]
disrupted by DA receptor antagonists. Libido can be increased by drugs that affect dopamine, but not
by drugs that affect opioid peptides or other neurotransmitters.
Learning, reinforcement, and reward-seeking behavior
Dopamine is commonly associated with the reward system of the brain, providing feelings of enjoyment
and reinforcement to motivate a person to perform certain activities. Dopamine is released (particularly in
areas such as the nucleus accumbens and prefrontal cortex) as a result ofrewarding experiences such
[41]
as food, sex, drugs, and neutral stimuli that become associated with them. Recent studies indicate
[42]
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 amphetamines, 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 withpsychological
[43]
dependence), arguing that this dopamine pathway is pathologically altered in addicted persons. In
recent studies, cholinergic inactivation of the nucleus accumbens was able to disrupt the acquisition of
drug reinforced behaviors, suggesting that dopamine has a more limited involvement in the acquisition of
both drug self-administration and drug-conditioned place-preference behaviors than previously
[44][45]
thought.
[41]
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,
[41]
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
[41]
addiction. Recent research suggests that the firing of dopaminergic neurons is motivational 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
[41]
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
[46]
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
[46]
reward values. The nonreward neurons are predominate in the dorsolateral area of the substantia nigra
[46]
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
[46]
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
[41]
accumbens and neostriatum using 6-hydroxydopamine. With this large reduction in dopamine, the rats
would no longer eat of 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 eat. In another study, mutant hyperdopaminergic (increased dopamine) mice show higher
[47]
"wanting" but not "liking" of sweet rewards. Mice who cannot synthesize dopamine are unable to feed
sufficiently to survive more than a few weeks after birth, but will feed normally and survive if administered
[48]
L-DOPA.
Dopamine modulates foraging behavior in animals, by activating brain systems registering reward when
[49]
food sources are found. When monkeys are given a highly palatable food, dopamine levels rise, but
levels then decline when the palatable food is available for prolonged periods of time and is no longer
[50]
novel.
Salience
Further information: Incentive salience
Dopamine may also have a role in the salience of potentially important stimuli, such as sources of reward
[51]
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
[citation needed]
as "wanting") as opposed to actual consummatory pleasure (commonly referred to as "liking").
Latent inhibition and creative drive
Dopamine in the mesolimbic pathway 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 lobes, the temporal lobes, and mesolimbic
[52]
dopamine.
Sociability
Since dopamine drives reward-seeking behavior and successive sensations of contentment from social
[53]
interactions, sociability is also closely tied to dopamine neurotransmission. Low D2 receptor-binding is
found in people with social anxiety. 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
[citation needed]
as hypersexual.
This is credited to an increase in dopamine, because mania can be reduced
[54]
by dopamine-blocking antipsychotics.
Processing of pain
Dopamine has been demonstrated to play a role in pain processing in multiple levels of the central
[55]
[56]
[57]
nervous system including the spinal cord, periaqueductal gray (PAG), thalamus, basal
[58][59]
[60][61]
[62]
ganglia,
insular cortex,
and cingulate cortex. Accordingly, decreased levels of dopamine have
[63]
been associated with painful symptoms that frequently occur in Parkinson's disease. Abnormalities in
dopaminergic neurotransmission have also been demonstrated in painful clinical conditions,
[64]
[65][66]
[67]
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
[68]
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 disorder, and
stimulant medications that are used to treat its symptoms increase dopamine
[69]
neurotransmission. Consistent with this hypothesis, dopaminergic pathways have a role in inhibitory
[70]
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
[71]
syndrome.
Dopaminergic mind hypothesis
The dopaminergic mind hypothesis seeks to explain the differences between modern humans and their
[72]
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 habilis, 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
[72]
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,
[72]
competition, and aggression than nurturance and communality." Although behavioral evidence and
some indirect anatomical evidence (e.g., enlargement of the dopamine-rich striatum in
[73]
humans) support a dopaminergic expansion in humans, there is still no direct evidence that dopamine
[74]
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
[75]
hypothesis.
Links to psychosis
Main article: Dopamine hypothesis of schizophrenia
[76]
Abnormally high dopaminergic transmission has been linked to psychosis and schizophrenia. However,
clinical studies relating schizophrenia to brain dopamine metabolism have ranged from controversial to
[77]
negative, with HVA levels in the CSF the same for schizophrenics and controls. 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
[citation needed]
seen in schizophrenia.
Antipsychotic medications 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[78]
called typical antipsychotics most commonly act on D2 receptors, while the atypical drugs also act on
[79][80]
D1, D3 and D4 receptors, though they have a lower affinity for dopamine receptors in general.
The
finding that drugs such as amphetamines, methamphetamine and cocaine, which can increase dopamine
[81]
levels by more than tenfold, can temporarily cause psychosis, provides further evidence for this
[82]
[83]
link. However, many non-dopaminergic drugs can induce acute and chronic psychosis. The NMDA
antagonists Ketamine and PCP both are used in research to reproduce the positive and negative
[84][85]
symptoms commonly associated with schizophrenia.
[86]
Dopaminergic dysregulation has also been linked to depressive disorders. Early research in humans
used various methods of analyzing dopamine levels and function in depressed patients. Studies have
reported that there is decreased concentration of tyrosine, a precursor to dopamine, in the blood plasma,
ventricular spinal fluid, and lumbar spinal fluid of depressed patients compared to control
[87] [88]
subjects.
One study measured the amount of homovanillic acid, the major metabolite of dopamine in
the CSF, as a marker for the dopamine pathway turnover rate, and found decreased concentrations of
[89]
homovanillic acid in the CSF of depressed patients. Postmordem real time reverse transcriptasepolymerase chain reaction (RT-PCR) has also been used to find that gene expression of a specific
subtype of dopamine receptor was elevated in the amygdale of people suffering from depression as
[90]
compared to control subjects.
The action of commonly used antidepressant drugs also has yielded information about possible
alterations of the dopaminergic pathway in treating depression. It has been reported that many
[91]
antidepressant drugs increase extracellular dopamine concentrations in the rat prefrontal cortex , but
[92] [93]
vary greatly in their affects on the striatum and nucleus accumbens.
This can be compared
to electro convulsive shock treatment (ECT), which has been shown to have a multiple fold increase in
[94]
striatal dopamine levels in rats.
More recent research studies with rodents have found that depression-related behaviors are associated
[95]
with dopaminergic system dysregulation. In rodents exposed to chronic mild stress, decreased escape
behavior and decreased forced swimming is reversed with activation of the dopaminergic mesolimbic
[96]
pathway. Also, rodents that are susceptible to depression-related behavior after social defeat can have
[97]
their behavior reversed with dopamine pathway activation. Depletion of dopamine in the caudate
nucleus and nucleus accumbens has also been reported in cases of learned helplessness in animals.
These symptoms can be reversed with dopamine agonists and antidepressant administration prior to the
[98]
learned helplessness protocol.
Therapeutic use
Under the trade names Intropan, Inovan, Revivan, Rivimine, Dopastat, and Dynatra, dopamine, as
well as norepinephrine and epinephrine, are also used as pharmaceutical drugs in injectable forms in
the emergency clinical treatment of severe hypotension and/or bradycardia, circulatory shock,
[citation needed]
and cardiac arrest, the latter of which for the purpose of cardiopulmonary resuscitation.
Levodopa is a dopamine precursor used in various forms to treat Parkinson's disease and doparesponsive 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.
Nonneural functions
Renal and cardiovascular
Dopamine (brand name Intropin or Giludop) also has effects when administered through an IV line
outside the central nervous system. The effects in this form are dose dependent.

Dopamine induces natriuresis (sodium loss) in the kidneys, and has a diuretic effect, potentially
[99][100]
increasing urine output from 5 ml/kg/hr to 10 ml/kg/hr.
Dosages from 2 to 5 μg/kg/min are
[101]
considered the "renal dose".
It was once thought that at this low dosage provided increased renal
perfusion in critically ill patients. The mechanism was thought to involve dopamine
binding D1 receptors, dilating blood vessels, increasing blood flow to renal, mesenteric,
[102]
and coronary arteries, which would thus increase overall renal perfusion.
However, recent multi[103]
center, randomized trials have shown that this is not clinically effective.
Thus, "renal dose"
dopamine is largely considered a myth that has been propagated in medicine for the past 30 years.

Intermediate dosages from 5 to 10 μg/kg/min, known as the "cardiac dose", additionally have a
positive inotropic and chronotropic effect through increased β1 receptor activation. Dopamine is used
[102]
in patients with shock or heart failure to increase cardiac output and blood pressure. Dopamine
[104]
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
[102]
through α1 receptor activation,
but can cause the vessels in the kidneys to constrict to the point
[105]
that urine output is reduced.
[105]
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 monocytes, moderate
expression on neutrophils and eosinophils, and high expression on B cells and natural killer
[106]
cells.
The sympathetic innervation of lymphoid tissues is dopaminergic, and increases during
[107]
stress.
Dopamine can also affect immune cells in the spleen, bone marrow, and blood
[108]
circulation.
In addition, dopamine can be synthesized and released by the immune cells
[109][110]
themselves.
The effects of dopamine on immune cells depend upon their physiological state. While dopamine
activates resting T cells, 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
[111]
dopamine signaling pathways, are also associated with altered immune functioning.
Toxicity
The LD50, or dose which is expected to be lethal in 50% of the population, has been found to be:
59 mg/kg (mouse; administered i.v.); 950 mg/kg (mouse; administered i.p.); 163 mg/kg (rat; administered
[112][clarification needed]
i.p.); 79 mg/kg (dog; administered i.v.)
In plants
Fruit browning
Polyphenol oxidases (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 quinones. The natural substrate for PPOs
inbananas is dopamine. The product of their oxidation, dopamine quinone, spontaneously oxidises to
other quinones. The quinones then polymerise and condense with amino acids and proteins to form
brown pigments known as melanins. The quinones and melanins derived from dopamine may help
[113]
protect damaged fruit and vegetables against growth of bacteria and fungi.
Anti-herbivore
Dopamine is released by the marine alga Ulvaria obscura as an anti-herbivore defense mechanism.
[114]
References
1.
^ Ian P. Stolerman (2 August 2010). Encyclopedia of Psychopharmacology, Volume 2. Springer
Publishing. ISBN 3-540-68698-3.
2.
^ "Dopamine - A Sample Neurotransmitter".
3.
^ Depue, R. A., & Collins, P. F. (1999). Neurobiology of the structure of personality: Dopamine, facilitation
of incentive motivation, and extraversion. Behavioral and Brain Sciences, 22, 491–517.
4.
^http://citation.allacademic.com/meta/p_mla_apa_research_citation/1/1/1/9/0/pages111906/p11190611.php
5.
^ [1] Davis, K.L., Kahn, R.S., Ko, G., Davidson, M. (1991) Dopamine in schizophrenia: a review and
reconceptualization. American Journal of Psychiatry 148:1474–1486.
6.
^ [2] Goldman-Rakic, P.S,. Castner, S.A., Svensson, T.H., Siever, L.J., Williams, G.V., (2004). Targeting
the dopamine D1 receptor in schizophrenia: insights for cognitive dysfunction. Psychopharmacology,174:
3–16
7.
^ "Patients' Brains May Adapt to ADHD Medication". Neuroscience News. April 4, 2012. Retrieved April 4,
2012.
8.
^ Allen, R (2004). "Dopamine and iron in the pathophysiology of restless legs syndrome (RLS)". Sleep
Medicine 5 (4): 385–91.doi:10.1016/j.sleep.2004.01.012. PMID 15222997.
9.
^ Clemens, S.; Rye, D; Hochman, S (2006). "Restless legs syndrome: Revisiting the dopamine hypothesis
from the spinal cord perspective". Neurology 67 (1): 125–
130.doi:10.1212/01.wnl.0000223316.53428.c9. PMID 16832090.
10. ^ Fahn, Stanley, "The History of Levodopa as it Pertains to Parkinson's disease," Movement Disorder
Society's 10th International Congress of Parkinson's Disease and Movement Disorders on November 1,
2006, in Kyoto, Japan.
11. ^ Benes, F.M. (2001). "Carlsson and the discovery of dopamine".Trends in Pharmacological
Sciences 22 (1): 46–47.doi:10.1016/S0165-6147(00)01607-2. PMID 11165672.
12. ^ J. Giesecke (1980). "Refinement of the structure of dopamine hydrochloride." Acta Cryst. Sect. B 36 178–
181.
13. ^ J. S. Bayeler, Ann. Chem., 513, 196 (1934).
14. ^ G. Hahn, K. Stiehl, Chem. Ber., 69, 2640 (1936).
15. ^ T. Kiss and A. Gergely (1979). "Complexes of 3,4-dhydroxyphenyl derivatives. III. Equilibrium study of
parent and some mixed ligand complexes of dopamine, alanine and pyrocatechol with nickel(II), copper(II)
and zinc(II) ions." Inorg. Chim. Acta 36 31-36.
16. ^ J. Armstrong and R. B. Barlow (1976). "The ionization of phenolic amines, including apomorphine,
dopamine and catecholamines and an assessment of zwitterion constants." Brit. J. Pharmacol. 57501-516.
17. ^ Biosensors and Bioelectronics 39 (2013) 124–132
18. ^ Morón, JA; Brockington, A; Wise, RA; Rocha, BA; Hope, BT (2002)."Dopamine uptake through the
norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from
knock-out mouse lines.". Journal of Neuroscience 22 (2): 389–95.PMID 11784783.
19. ^ Yavich, L; Forsberg, MM; Karayiorgou, M; Gogos, JA; Männistö, PT (2007). "Site-specific role of catecholO-methyltransferase in dopamine overflow within prefrontal cortex and dorsal striatum.".Journal of
Neuroscience 27 (38): 10196–209.doi:10.1523/JNEUROSCI.0665-07.2007. PMID 17881525.
20. ^ /http://www.dukehealth.org/health_library/news/9904
21. ^ Peter Redgrave, Kevin Gurney (2006). "The short-latency dopamine signal: a role in discovering novel
actions?". Nature Reviews Neuroscience 7 (12): 967–975. doi:10.1038/nrn2022.PMID 17115078.
22. ^ Predictive reward signal of dopamine neurons - 2005: By signaling rewards according to a prediction
error, dopamine responses have the formal characteristics of a teaching signal postulated by reinforcement
learning theories
23. ^ Barron AB, Maleszka R, Vander Meer RK, Robinson GE (2007)."Octopamine modulates honey bee
dance behavior". Proc. Natl. Acad. Sci. U.S.A. 104 (5): 1703–
7. doi:10.1073/pnas.0610506104.PMC 1779631. PMID 17237217.
24. ^ Schwaerzel M, Monastirioti M, Scholz H, Friggi-Grelin F, Birman S, Heisenberg M (November
2003). "Dopamine and octopamine differentiate between aversive and appetitive olfactory memories in
Drosophila". J. Neurosci. 23 (33): 10495–502. PMID 14627633.
25. ^ Selcho M, Pauls D, Han KA, Stocker RF, Thum AS (2009). "The role of dopamine in Drosophila larval
classical olfactory conditioning". In Giurfa, Martin. PLoS ONE 4 (6):
e5897.doi:10.1371/journal.pone.0005897. PMC 2690826.PMID 19521527.
26. ^ Schultz, Cambridge university, UK
27. ^ Bjorklund A, Dunnett SB (2007). "Dopamine neuron systems in the brain: an update". Trends in
Neurosciences 30 (5): 194–202.doi:10.1016/j.tins.2007.03.006. PMID 17408759.
28. ^ Grace AA, (1991). "Phasic versus tonic dopamine release and the modulation of dopamine system
responsivity: A hypothesis for the eitiology of schizophrenia" (PDF). Neuroscience 41 (1): 1–
24.doi:10.1016/0306-4522(91)90196-U. PMID 1676137.
29. ^ Grace AA, Bunney BS (1984). "The control of firing pattern in nigral dopamine neurons: single spike
firing" (PDF). Journal of Neuroscience 4 (11): 2866–2876. PMID 6150070.
30. ^ Grace AA, Bunney BS (1984). "The control of firing pattern in nigral dopamine neurons: burst
firing" (PDF). Journal of Neuroscience 4(11): 28677–2890. PMID 6150071.
31. ^ Gonon FG (1988). "Nonlinear relationship between impulse flow and dopamine released by rat midbrain
dopaminergic neurons as studied by in vivo electrochemistry" (PDF). Neuroscience 24 (1): 19–
28. doi:10.1016/0306-4522(88)90307-7. PMID 3368048.
32. ^
a b
http://www.australianprescriber.com/magazine/17/1/17/21
33. ^ Ben-Jonathan N, Hnasko R (2001). "Dopamine as a Prolactin (PRL) Inhibitor" (PDF). Endocrine
Reviews 22 (6): 724–763.doi:10.1210/er.22.6.724. PMID 11739329.
34. ^ Heijtz RD, Kolb B, Forssberg H (2007). "Motor inhibitory role of dopamine D1 receptors: implications for
ADHD" (PDF). Physiol Behav 92 (1–2): 155–160. doi:10.1016/j.physbeh.2007.05.024.PMID 17585966.
35. ^ Browman, KE; Curzon, P; Pan, JB; Molesky, AL; Komater, VA; Decker, MW; Brioni, JD; Moreland, RB et
al. (2005). "A-412997, a selective dopamine D4 agonist, improves cognitive performance in
rats". Pharmacology, Biochemistry, and Behavior 82 (1): 148–
55.doi:10.1016/j.pbb.2005.08.002. PMID 16154186.
36. ^ Lambert M, Schimmelmann B, Karow A, Naber D (2003). "Subjective well-being and initial dysphoric
reaction under antipsychotic drugs - concepts, measurement and clinical
relevance". Pharmacopsychiatry 36 (Suppl 3): S181–90.doi:10.1055/s-2003-45128. PMID 14677077.
37. ^ Raji, Y.; Ifabunmi, S.O.; Akinsomisoye, O.S.; Morakinyo, A.O.; Oloyo, A.K. (2005). "Gonadal Responses
to Antipsychotic Drugs: Chlorpromazine and Thioridazine Reversibly Suppress Testicular Functions in
Albino Rats". International Journal of Pharmacology 1(3):
287292. doi:10.3923/ijp.2005.287.292. ISSN 18117775.
38. ^ Lemke M, Brecht H, Koester J, Kraus P, Reichmann H (2005)."Anhedonia, depression, and motor
functioning in Parkinson's disease during treatment with pramipexole". J Neuropsychiatry Clin
Neurosci 17 (2): 214–20.doi:10.1176/appi.neuropsych.17.2.214. PMID 15939976.
39. ^ Peciña S, Berridge K (2005). "Hedonic hot spot in nucleus accumbens shell: where do mu-opioids cause
increased hedonic impact of sweetness?". J Neurosci 25 (50): 11777–86.doi:10.1523/JNEUROSCI.232905.2005. PMID 16354936.
40. ^ Pfaus J, Phillips A (1991). "Role of dopamine in anticipatory and consummatory aspects of sexual
behavior in the male rat". Behav Neurosci 105 (5): 727–43. doi:10.1037/07357044.105.5.727.PMID 1840012.
41. ^
a b c d e f
Arias-Carrión O, Pöppel E (2007). "Dopamine, learning and reward-seeking behavior". Act
Neurobiol Exp 67 (4): 481–488.
[dead link]
42. ^ Dopamine Involved In Aggression - Medical News Today
43. ^ Eric J. Nestler, Department of Psychiatry and Center for Basic Neuroscience, The University of Texas
Southwestern Medical Center (2005). "Is There A Common Molecular Pathway For Addiction?".Nature
Neuroscience 8 (11): 1445–1449. doi:10.1038/nn1578.PMID 16251986.
44. ^ Crespo, JA; Sturm K, Saria A, Zernig G (May 2006). "Activation of Muscarinic and Nicotinic Acetylcholine
Receptors in the Nucleus Accumbens Core Is Necessary for the Acquisition of Drug
Reinforcement". Journal of Neuroscience.
45. ^ Witten, I.B.; Lin S-C,Brodsky M., Prakash, R., Dieste, I., Anikeeva, P., Gradinaru, V., Ramakrishnan C. &
Deisseroth, K. (December 2010). "Cholinergic Interneurons Control Local Circuit Activity and Cocaine
Conditioning". Science 330 (6011): 1677–81.doi:10.1126/science.1193771. PMC 3142356.PMID 21164015.
46. ^
a b c d
Matsumoto M, Hikosaka O. (2009). "Two types of dopamine neuron distinctly convey positive and
negative motivational signals". Nature 459 (7248): 837–
41. doi:10.1038/nature08028.PMC 2739096. PMID 19448610.
47. ^ Peciña S, Cagniard B, Berridge K, Aldridge J, Zhuang X (2003). "Hyperdopaminergic mutant mice have
higher "wanting" but not "liking" for sweet rewards". J Neurosci 23 (28): 9395–402.PMID 14561867.
48. ^ Szczypka, M. S., Rainey, M. A., & et al (1992). "behavior in dopamine-deficient mice". PNAS 96 (21):
12142–12143.doi:10.1073/pnas.96.21.12138.
49. ^http://onlinelibrary.wiley.com/doi/10.1207/s15516709cog0000_50/abstract
50. ^ http://www.jneurosci.org/content/13/3/900.full.pdf
51. ^ Schultz W (2002). "Getting formal with dopamine and reward".Neuron 36 (2): 241–
263. doi:10.1016/S0896-6273(02)00967-4.PMID 12383780.
52. ^ Flaherty, A.W, (2005). "Frontotemporal and dopaminergic control of idea generation and creative
drive". Journal of Comparative Neurology 493 (1): 147–
153. doi:10.1002/cne.20768.PMC 2571074. PMID 16254989.
53. ^ Poquérusse, Jessie. "The Neuroscience of Sharing". Retrieved 16 August 2012.
54. ^ http://bipolar.about.com/cs/menu_treat/a/0312_treatmania_3.htm
55. ^ Jensen, TS; Yaksh, TL. (1984). "Effects of an intrathecal dopamine agonist, apomorphine, on thermal and
chemical evoked noxious responses in rats". Brain Res. 296 (2): 285–93. doi:10.1016/0006-8993(84)900647. PMID 6322926.
56. ^ Flores, JA; El Banoua, F; Galán-Rodríguez, B; Fernandez-Espejo, E. (2004). "Opiate anti-nociception is
attenuated following lesion of large dopamine neurons of the periaqueductal grey: critical role for D1 (not
D2) dopamine receptors". Pain 110 (1–2): 205–14.doi:10.1016/j.pain.2004.03.036. PMID 15275769.
57. ^ Shyu, BC; Kiritsy-Roy, JA; Morrow, TJ; Casey, KL. (1992). "Neurophysiological, pharmacological and
behavioral evidence for medial thalamic mediation of cocaine-induced dopaminergic analgesia". Brain
Res 572 (1–2): 216–23. doi:10.1016/0006-8993(92)90472-L. PMID 1611515.
58. ^ Chudler, EH; Dong, WK. (1995). "The role of the basal ganglia in nociception and pain". Pain 60 (1): 3–
38. doi:10.1016/0304-3959(94)00172-B. PMID 7715939.
59. ^ Altier, N; Stewart, J. (1999). "The role of dopamine in the nucleus accumbens in analgesia". Life
Sci. 65 (22): 2269–87.doi:10.1016/S0024-3205(99)00298-2. PMID 10597883.
60. ^ Burkey, AR; Carstens, E; Jasmin, L. (1999). "Dopamine reuptake inhibition in the rostral agranular insular
cortex produces antinociception". J Neurosci 19 (10): 4169–79. PMID 10234044.
61. ^ Coffeen, U; López-Avila, A; Ortega-Legaspi, JM; Angel, R; López-Muñoz, FJ; Pellicer, F. (2008).
"Dopamine receptors in the anterior insular cortex modulate long-term nociception in the rat". Eur J
Pain.12 (5): 535–43. doi:10.1016/j.ejpain.2007.08.008.PMID 17936656.
62. ^ López-Avila, A; Coffeen, U; Ortega-Legaspi, JM; Angel, R; Pellicer, F. (2004). "Dopamine and NMDA
systems modulate long-term nociception in the rat anterior cingulate cortex". Pain 111 (1–2): 136–
43. doi:10.1016/j.pain.2004.06.010. PMID 15327817.
63. ^ Brefel-Courbon, C; Payoux, P; Thalamas, C; Ory, F; Quelven, I; Chollet, F; Montastruc, JL; Rascol, O.
(2005). "Effect of levodopa on pain threshold in Parkinson's disease: a clinical and positron emission
tomography study". Mov Disord 20 (12): 1557–63.doi:10.1002/mds.20629. PMID 16078219.
64. ^ Jääskeläinen, SK; Rinne, JO; Forssell, H; Tenovuo, O; Kaasinen, V; Sonninen, P; Bergman, J. (2001).
"Role of the dopaminergic system in chronic pain -- a fluorodopa-PET study". Pain 90 (3): 257–
60. doi:10.1016/S0304-3959(00)00409-7. PMID 11207397.
65. ^ Wood, PB; Patterson Jc, 2nd; Sunderland, JJ; Tainter, KH; Glabus, MF; Lilien, DL (2007). "Reduced
presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: a
pilot study". J Pain 8 (1): 51–8.doi:10.1016/j.jpain.2006.05.014. PMID 17023218.
66. ^ Wood, PB; Schweinhardt, P; Jaeger, E; Dagher, A; Hakyemez, H; Rabiner, EA; Bushnell, MC; Chizh, BA.
(2007). "Fibromyalgia patients show an abnormal dopamine response to pain". Eur J Neurosci 25(12):
3576–82. doi:10.1111/j.1460-9568.2007.05623.x.PMID 17610577.
67. ^ Cervenka, S; Pålhagen, SE; Comley, RA; Panagiotidis, G; Cselényi, Z; Matthews, JC; Lai, RY; Halldin, C
et al. (2006). "Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor
binding". Brain 129 (Pt 8): 2017–28.doi:10.1093/brain/awl163. PMID 16816393.
68. ^ Wood, PB. (2008). "Role of central dopamine in pain and analgesia". Expert Rev Neurother 8 (5): 781–
97.doi:10.1586/14737175.8.5.781. PMID 18457535.
69. ^ "A dynamic developmental theory of attention-deficit/hyperactivity disorder (ADHD) predominantly
hyperactive/impulsive and combined subtypes". Cambridge Journals. Retrieved 2009-04-20.
70. ^ Colzato, LS; Van Den Wildenberg, WP; Van Wouwe, NC; Pannebakker, MM; Hommel, B
(2009). "Dopamine and inhibitory action control: evidence from spontaneous eye blink rates".Experimental
brain research. Experimentelle Hirnforschung. Experimentation cerebrale 196 (3): 467–
74. doi:10.1007/s00221-009-1862-x. PMC 2700244. PMID 19484465.
71. ^ Merims D, Giladi N (2008). "Dopamine dysregulation syndrome, addiction and behavioral changes in
Parkinson's disease".Parkinsonism & Related Disorders 14 (4): 273–
80.doi:10.1016/j.parkreldis.2007.09.007. PMID 17988927.
72. ^
a b c
Previc F (2009). The Dopaminergic Mind in Human Evolution and History Cambridge University
Press. ISBN 978-0-521-51699-0.
73. ^ Rapoport, S. I. (1990). "Integrated phylogeny of the primate brain, with special reference to humans and
their diseases". Brain Research Reviews 15 (3): 267–294. doi:10.1016/0165-0173(90)900048. PMID 2289087.
74. ^ Raghanti, M. A.; Stimpson, C. D.; Marcinkiewicz, J. L.; Erwin, J. M.; Hof, P. R.; Sherwood, C. C.
(2008a). "Cortical dopaminergic innervation among humans, chimpanzees, and macaque monkeys: A
comparative study". Neuroscience 155 (1): 203–
20.doi:10.1016/j.neuroscience.2008.05.008. PMC 3177596.PMID 18562124.
75. ^ http://www.scientificamerican.com/article.cfm?id=interactive-seas-saved-humanity
76. ^ "Disruption of gene interaction linked to schizophrenia". St. Jude Children's Research Hospital. Retrieved
2006-07-06.
77. ^ Maas, J.W.; Bowden CL, Miller AL, Javors MA, Funderburg LG, Berman N, Weintraub ST. (1997).
"Schizophrenia, psychosis, and cerebral spinal fluid homovanillic acid concentrations.".Schizophrenia
Bulletin. 23 (1): 147–154. PMID 9050120.
78. ^ http://www.williams.edu/imput/synapse/pages/IIIB5.htm
79. ^ http://bjp.rcpsych.org/cgi/content/full/181/4/271
80. ^ Durcan, M; Rigdon, GC; Norman, MH; Morgan, PF (1995). "Is clozapine selective for the dopamine D4
receptor?". Life Sciences 57(18): PL275–83. doi:10.1016/0024-3205(95)02151-8.PMID 7475902.
81. ^ Methamphetamine 101
82. ^ Lieberman, J.A.; JM Kane, J. Alvir (1997). "Provocative tests with psychostimulant drugs in
schizophrenia". Psychopharmacology (Berl). 91 (4): 415–433. doi:10.1007/BF00216006.PMID 2884687.
83. ^ Cardinal, R.N. & Bullmore, E.T., The Diagnosis of Psychosis,Cambridge University Press, 2011, ISBN
978-0-521-16484-9
84. ^ The Neuropsychopharmacology of Phencyclidine: From NMDA Receptor Hypofunction to the Dopamine
Hypothesis of Schizophrenia
85. ^ Abi-Saab, WM; D'Souza DC, Moghaddam B, Krystal JH (1998). "The NMDA antagonist model for
schizophrenia: promise and pitfalls.". Pharmacopsychiatry 31 (2): 104–109. doi:10.1055/s-2007979354. PMID 9754841.
86. ^ Galani, VJ; Rana DG (2011). "Depression and antidepressants with dopamine hypothesis-A
review". IJPFR 1 (2): 45–60.
87. ^ Denkert, O; Renz A, Marano C, Matussek N. (1971). "Altered tyrosine daytime plasma levels in
edogenous depressed patients".Arch gen Psychiat 25: 359–363.
88. ^ Birkmayer, W; Linauer W, Storung D (1970). "Tyrosin and tryptophan- metabolisms in depression
patients". Arch Psychiar Nervenkr 213: 377–387.
89. ^ Bowers, MB; Heninger GR, Gerbode F. (1969). "Cerebrospinal fluid 5-hydroxyindoleacetic acid and
homovanillic acid in psychiatric patients". Int J Neuropharmacol 8: 255–262.
90. ^ Lianbin, X; Katalin S, Attila S, Violetta K, Craig A, Stockmeier C, Beata K, John K, Gregory A, Ordwaya
(2008). "Dopamine receptor gene expression in human amygdaloid nuclei: Elevated D4 receptor mRNA in
major depression". Brain Res 1207: 214–224.
91. ^ Carlson, JN; Visker KE, Nielsen DM, Keller RW, Glick SD (1996). "Chronic antidepressant drug treatment
reduces turning behavior and increases dopamine levels in the medial prefrontal cortex".Brain Res 707:
122–126.
92. ^ Ainsworth, K; Smith SE, Zetterstrom TS, Pei Q, Franklin M, Sharp T (1998). "Effect of antidepressant
drugs on dopamine D1 and D2 receptor expression and dopamine release in the nucleus accumbens of the
rat". Psychopharmacology 140: 470–477.
93. ^ Meltzer, TL; Wiley JN, Williams AE, Heffner TG (1988). "Evidence for postsynaptic dopamine effects of BHT 920 in the presence of the dopamine D1 agonist SKF 38393". Psychopharmacology 95: 329–332.
94. ^ Nomikos, GG; Damsma G, Wenkstern D, Fibiger HC (1989). "Acute effects of bupripion on extracellular
dopamine concentration in rat striatum and nucleus accumbens studies by in vivo microdialysis
study". Neuropsychopharmacol 4: 65–69.
95. ^ Tye; Mirzabekov, Warden, Ferenczi, Tsai, Finkelstein, kim, Adhikari, Thompson, Andalman, Gunaydin,
Witten & Deisseroth (2012). "Dopamine neurons modulate neural encoding and expression of depressionrelated behaviour". Nature 493: 537–541.
96. ^ Tye; Mirzabekov, Warden, Ferenczi, Tsai, Finkelstein, kim, Adhikari, Thompson, Andalman, Gunaydin,
Witten & Deisseroth (2012). "Dopamine neurons modulate neural encoding and expression of depressionrelated behaviour". Nature 493: 537–541.
97. ^ Chaudhury, D; Walsh, Friedman, Juarez, Ku, Koo, Ferguson, Tsai, Pomeranz, Christoffel, Nectow,
Ekstrand, Domingos, Mazei-Robison, Mouzon, Lobo, Neve, Friedman, Russo, Deisseroth, Nestler, Han
(2013). "Rapid regulation of depression-related behaviors by control of midbrain dopamine
neurons". Nature 493: 532–536.
98. ^ Muscat, R; Sampson D, Willner P. (1990). "Dopaminergic mechanisms of imipramine action in an animal
model of depression". Biol Psychiatry 28: 223–230.
99. ^ Gildea, John J (2009). "Dopamine and angiotensin as renal counterregulatory systems controlling sodium
balance". Current Opinion in Nephrology and Hypertension 18 (1): 28–
32.doi:10.1097/MNH.0b013e32831a9e0b. PMC 2847451.PMID 19077686.
100. ^ Cinelli, A. R.; Efendiev, R.; Pedemonte, C. H. (2008). "Trafficking of Na-K-ATPase and dopamine receptor
molecules induced by changes in intracellular sodium concentration of renal epithelial cells". AJP: Renal
Physiology 295 (4): F1117–25.doi:10.1152/ajprenal.90317.2008. PMC 2576148.PMID 18701625.
101. ^ "Renal Vasodilatory Action of Dopamine in Patients With Heart Failure: Magnitude of Effect and Site of
Action". Circulation. 2008;117:200-205. Retrieved 2009-04-20.
102. ^
a b c
Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview.
p. 8. ISBN 1-59541-101-1.
103. ^ Holmes CL (2003). Bad medicine: low-dose dopamine in the
ICU.http://www.ncbi.nlm.nih.gov/pubmed/12684320.
104. ^ "Dopamine and Dextrose". Drugs.com. Retrieved 2009-04-20.
105. ^
a b
Bronwen Jean Bryant; Kathleen Mary Knights (15 November 2009). Pharmacology for Health
Professionals (2nd ed.). Elsevier Australia. p. 192. ISBN 978-0-7295-3929-6. Retrieved 9 June 2011.
106. ^ McKenna, F; McLaughlin, PJ; Lewis, BJ; Sibbring, GC; Cummerson, JA; Bowen-Jones, D; Moots, RJ.
(2002). "Dopamine receptor expression on human T- and B-lymphocytes, monocytes, neutrophils,
eosinophils and NK cells: a flow cytometric study". J Neuroimmunol 132 (1–2): 34–40. doi:10.1016/S01655728(02)00280-1. PMID 12417431.
107. ^ Mignini, F; Streccioni, V; Amenta, F (2003). "Autonomic innervation of immune organs and neuroimmune
modulation". Autonomic & autacoid pharmacology 23 (1): 1–25. doi:10.1046/j.14748673.2003.00280.x. PMID 14565534.
108. ^ Basu, S; Dasgupta, PS. (2000). "Dopamine, a neurotransmitter, influences the immune system". J
Neuroimmunol 102 (2): 113–24.doi:10.1016/S0165-5728(99)00176-9. PMID 10636479.
109. ^ Bergquist, J; Tarkowski, A; Ekman, R; Ewing, A. (1994). "Discovery of endogenous catecholamines in
lymphocytes and evidence for catecholamine regulation of lymphocyte function via an autocrine loop". Proc
Natl Acad Sci U S A 91 (26): 12912–6.doi:10.1073/pnas.91.26.12912. PMC 45550. PMID 7809145.
110. ^ Cosentino, M; Fietta, AM; Ferrari, M; Rasini, E; Bombelli, R; Carcano, E; Saporiti, F; Meloni, F et al.
(2007). "Human CD4+CD25+ regulatory T cells selectively express tyrosine hydroxylase and contain
endogenous catecholamines subserving an autocrine/paracrine inhibitory functional loop". Blood 109 (2):
632–42. doi:10.1182/blood-2006-01-028423. PMID 16985181.
111. ^ Sarkar, C; Basu, B; Chakroborty, D; Dasgupta, PS; Basu, S (2010)."The immunoregulatory role of
dopamine: an update". Brain, behavior, and immunity 24 (4): 525–
8.doi:10.1016/j.bbi.2009.10.015. PMC 2856781.PMID 19896530.
112. ^ R. J. Lewis (Ed.) (2004), Sax's Dangerous Properties of Industrial Materials, 11th Ed., p. 1552, Wiley &
Sons, Hoboken, NJ.
113. ^ Mayer, AM (2006). "Polyphenol oxidases in plants and fungi: Going places? A
review". Phytochemistry 67 (21): 2318–2331.doi:10.1016/j.phytochem.2006.08.006. PMID 16973188.
114. ^ Van Alstyne, Kathryn L.; Nelson, Amorah V.; Vyvyan, James R.; Cancilla, Devon A. (2006). "Dopamine
functions as an antiherbivore defense in the temperate green alga Ulvaria obscura". Oecologia148 (2): 304–
311. doi:10.1007/s00442-006-0378-3.PMID 16489461. Retrieved December 29, 2011.