The 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 "

Dr. Keti:
March 20, 2003

Dopamine
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 movie

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

Physiology 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.

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What 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

Low Dopamine 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 with walking.

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 presence. (7)

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 questionable, Alexander 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 Parkinsonian symptoms.

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.

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Parkinsonian symptoms 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 disease. (7)

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", homeostatic 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.

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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.

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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 enhance results.

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).

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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 (ref. 9)

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.

Lastly
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.

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