Question: "…For the past six months, I have been through
a battery of tests. Most thought I had an autoimmune or movement
disorder based on my symptoms. Fortunately or unfortunately, all
tests were normal with the exception of serum serotonin and dopamine.
I have little or none. We have, of course, rerun the test numerous
times. I am willing to send list of symptoms if you need. Anything
you can add/ suggest will help "
March 20, 2003
Dopamine is a neurotransmitter; a chemical messenger
that plays an active role between nerve cells in the mammalian brain
and in addiction (ref. 1 & 1.1.) Neurotransmission
Dopamine affects the brain processes
that control movement, emotional response, and ability to experience
pleasure and pain. It is believed that regulation of dopamine plays
a crucial role in our mental and physical health.
Neurons containing the neurotransmitter
dopamine are clustered in the part of the brain, an area called
the substantia nigra.
The brain works through neurons
that communicate with each other and release chemicals that produce
signals. These chemical messengers are called neurotransmitters.
When the Central Nervous System
generates repeated stimuli, dopamine, one of the neurotransmitters,
is released from the neural endings into the synapses,
the tiny spaces between the neurons. Neurotransmitters are repeatedly
secreted and reabsorbed back into the nervous cells endings. This
process helps continuing transmission of nervous stimuli traveling
along the nervous system cells (called neurons) and their branching
paths, see Dopamine
- A Sample Neurotransmitter
and Pathophysiology of Dopamine
The metabolism of dopamine is quite complex and in short, when dopamine
is released from the neural endings into the synapses, dopamine receptors are needed
to bind the released transmitter. The receptors are distinctly
shaped areas, proteins by structure, that are located on the surfaces
of the nerve cells.
The dopamine binds to its matching
receptors, triggers signals that either allow the message to be
passed on to other cells or prevent the message from being forwarded.
The dopamine that is not utilized
gets reabsorbed back into the dopamine producing neurons. Re-uptake
occurs in order to keep neurotransmitter levels steady and maintain
homeostasis (the inner body equilibrium), as this is the
body’s way of signaling the Central Nervous System (CNS) to
stop producing more of this neurotransmitter, a process called
negative feedback. To compensate for this and maintain the
equilibrium, the human body produces more dopamine receptors in
other places, i.e. on other neurons.
Influences Dopamine Levels?
There are many drugs that influence the amount of dopamine that
is released in the synapse and some enzymes such as monoamine
oxidase (MAO) break down dopamine.
The drugs that bind to dopamine
receptors and stimulate the same are called agonist. In
contrast to dopamine agonists, dopamine antagonists are
drugs that bind, but don't stimulate dopamine receptors. Antagonists
can prevent or reverse the actions of dopamine by keeping dopamine
from attaching to receptors.
Other drugs, such as cocaine
and amphetamine, produce their effects by affecting
the flow of neurotransmitters. Although both these drugs
increase the amount of dopamine in the synapse, cocaine achieves
this action by preventing dopamine Re-uptake, as does the drug
Methylphenidate, while amphetamine helps to release more dopamine.
The human body always tries to achieve and maintain
equilibrium (homeostasis), therefore once the dopamine receptors
are destroyed it stimulates the human body to produce more of the
receptors or the remaining receptors become more sensitive to dopamine,
a process that is called sensitization.
As one can imagine, opposite happens after dopamine
or dopamine agonists repeatedly stimulate dopamine receptors. Here
over stimulation decreases the number of receptors, and the remaining
receptors become less sensitive to dopamine. This process is called
desensitization or tolerance
Levels and Other Conditions
It is known that people with
Parkinson's disease lose neurons that contain dopamine,
i.e. the dopamine - transmitting neurons die in this area.
As a result, the brains of people with Parkinson's disease contain
almost no dopamine.
People with Parkinson's disease
(PD) suffer increasing motor behavior impairment, usually manifested
at an older age. The primary symptoms include muscular rigidity,
resting tremor, difficulty with movement initiation (bradykinesia),
slowness of voluntary movement, difficulty with balance, and difficulty
It is difficult to diagnose Parkinson's
disease in an early stage. The earliest symptoms may be non-specific,
such as weakness, tiredness, and fatigue.
Today there are no conclusive tests for Parkinson's
disease, yet there are several methods for evaluating its possible
A first diagnosis is based on an evaluation of
the presence and severity of the primary symptoms.
If this test is significant, a trial test of anti-parkinsonian
drugs may be used to further diagnose the presence of PD. This test
is usually performed with L-Dopa.
L-Dopa is a precursor in the biosynthesis of dopamine in nerve cells,
and causes the remaining dopamine producing cells to increase the
production of dopamine. Many doctors argue that if the patient fails
to benefit from L-Dopa, the diagnosis of Parkinson's disease is
van den Bosch (7)
Computed tomography (CT) or magnetic resonance
imaging (MRI) scans of the brain are used in helping to rule out
other diseases whose symptoms resemble Parkinson's disease, so-called
Some people who use drugs, that
they obtain on the street may exhibit Parkinsonian symptoms. There
are documented cases of young people using an illegal synthetic
drug that was contaminated with the toxic substance called MPTP
(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). This contaminant
induced Parkinson's disease in those who were
exposed to the same.
MPTP is a known industrial
toxin and is produced as by product in the event of sloppy synthesis
of MPPP (1-methyl-4-phenyl-4-propionpiperidine), the primary street
analog of meperidine, one of the so-called designer
drugs. Designer drugs are analogs of known pharmacological
agents, synthesized by underground chemists and sold and distributed
on the street. (8)
MPTP affects the dopaminergic neurons. MPTP is
a very specific neurotoxin, which can induce irreversible Parkinson's
symptoms at any age.
may be caused by a brain tumor, repeated head trauma, or prolonged
use of certain drugs. These diseases should not be confused
with Parkinson's disease.
Some viral infections
are known to damages the part of nervous system and cause Parkinson's
There are other diseases that are known to be associated
with low level of dopamine. Research studies indicate, that people
with so-called restless legs syndrome,
a condition associated with prickly, creepy-crawly sensation in
the legs and an irresistible urge to jerk about particularly while
trying to sleep, have abnormally low iron in the substantia nigra
(part of the brain) and it appears that dopamine activity is impaired
in the brain areas called putamen and caudate nucleus.
While reviewing literature, in the article under
the title of Low
dopamine D (2) receptor binding potential in social phobia
(3), a condition referred to as Generalized Social
Phobia may be associated with low binding of neurotransmitters
to their receptors or low levels of neurotransmitters produced by
the nervous cell endings.
Another paper that studies and presents what it calls "a self-replicating phenomenon",
called M0 ) suggests that excess
dopamine is secreted after a period of boredom, therefore according
to these researchers simply continuing to do nothing interesting
can produce an excess of dopamine!
The above-mentioned study argues that engaging
in high intensity exercise may only make
you feel worse, both mentally and physically, if you haven't had
the proper rest or nutrition.
It is a common knowledge that if you feel physically
wiped out, you can rejuvenate your mind and body by exercising or taking a
walk. These activities tend to increase the level of dopamine
in the synapse. Much of the new research suggests that
a balanced exercise activity positively affects
hippocampus a brain structure that is vital for memory
and learning .
Also recent studies indicate that challenging environments,
such as learning opportunities, social interactions and generally
being physically active, are key to boosting the growth of new brain
cells. One group of studies suggests that an active lifestyle plays
an important role in maintaining the function of the brain.
Serotonin and its Role
Serotonin is another neurotransmitter, also know
as feel-good neurotransmitter involved in the ability to
resist impulses, plays a major role in emotional disorders such
as depression, suicide, impulsive behavior, and aggression.
Serotonin is also involved in temperature regulation,
sensory perception, and mood control.
Neurons using serotonin as a neurotransmitter are
found in the part of brain called midbrain, primarily in
a cluster of cells called the pons. Tryptophan, an essential
amino acid, is the precursor to Serotonin.
Low levels of Tryptophan have been documented in
autistic children and in chronic pain
caused from arthritis and lower back problems.
It is thought that lower Serotonin levels have an effect on lowering
the pain tolerance threshold. Some nutritionists recommend a high
carbohydrate diet to increase Tryptophan metabolism, along with
Vitamin B6. D-Phenylalanine is also recommended in some cases to
Some recent studies found that Paroxetine,
a drug sold under the brand name Paxil, belonging to a class of anti-depressant drugs known
Selective Serotonin Re-uptake Inhibitors, or SSRIs, is believed
to relieve symptoms of depression by increasing the availability
of serotonin. The new findings suggest that this drug can also lead
to changes in personality characteristics(4).
One article on BBC, Does Love Drive You Mad?
refers to recent findings that one symptom of 'Obsessive Compulsive
Disorder' (OCD) appears to be associated with unusually low
levels of serotonin and that Italian students who claimed they had
recently fallen in love were found to have serotonin levels 40%
lower than their peers (ref.5)
From animal studies, scientists discovered that
low serotonin levels might be associated with impulsive or risky
behavior. Some researchers (6) now believe that
suicide may be the ultimate act of inwardly directed impulsive aggression. It has been shown through different studies, supported by brain
imaging called positron emission tomography (pet), that people who
suffer from severe depression have a very blunted response to the
neurotransmitter or very low serotonin levels www.utexas.edu
Some drugs like Prozac and the other drugs used
to treat severe depression prevent the normal Re-uptake of serotonin
others like the hallucinogenic drug LSD acts on serotonin receptors.
Serotonin production is also affected by hormone
such as estrogen. So, through complicated feedback loop
mechanism low estrogen is related to low serotonin, which tends
to cause cravings, mainly for high-carbohydrate, high-sugar content
foods (chocolate, cakes etc).
Serotonin is also the precursor for another important
hormone called melatonin. Melatonin is believed to influence
our sleep habits. Where low serotonin is present less melatonin
is produced in the pineal gland, influencing the sleep pattern,
and causing sleep problems.
Low serotonin is also associated with bulimia,
a severe eating disorder.
Your doctor should help you exclude known conditions that are related
to low levels of serotonin and dopamine.
Appropriate treatment may include simple changes
in your lifestyle, physical and social activities in addition to
any medication that you may have to take.