Biology 202
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Serotonin and Its Uses

Andrea Byrd

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter in the brain that has an enormous influence over many brain functions. It is synthesized, from the amino acid L-tryptophan, in brain neurons and stored in vesicles. Serotonin is found in three main areas of the body: the intestinal wall; large constricted blood vessels; and the central nervous system. The most widely studied effects have been those on the central nervous system. The functions of serotonin are numerous and appear to involve control of appetite, sleep, memory and learning, temperature regulation, mood, behavior (including sexual and hallucinogenic behavior), cardiovascular function, muscle contraction, endocrine regulation, and depression (1).

The activity of serotonin arises in the brainstem from clusters of neurons known as the raphe nucleus. From the brain, serotonin neurons extend to virtually all parts of the central nervous system making the branching of the serotonin network the most expansive neurochemical system in the brain. The importance of this network becomes apparent when considering each serotonin neuron exerts an influence over as many as 500,000 target neurons. Due to the widespread distribution of serotonin in the nervous system, it is not surprising that this neurotransmitter can be linked to many types of behavior (2).

Of the chemical neurotransmitter substances, serotonin is perhaps the most implicated in the treatment of various disorders, including anxiety, depression, obsessive-compulsive disorder, schizophrenia, stroke, obesity, pain, hypertension, vascular disorders, migraine, and nausea. A major factor in the understanding of the role of 5-HT in these disorders is the recent rapid advance made in understanding the physiological role of various serotonin receptor subtypes. There are at least four populations of receptors for serotonin: 5-HT1, 5-HT2, 5-HT3, and 5-HT4. The physiological function of each receptor subtype has not been established and is currently the subject of intensive investigation (1).

The linkage of serotonin to depression has been known for the past five years. From numerous studies, the most concrete evidence of this connection is the decreased concentration of serotonin metabolites like 5-HIAA (5-hydroxyindole acetic acid) in the cerebrospinal fluid and brain tissues of depressed people. If depression, as suggested, is a result of decreased levels of serotonin in the brain, pharmaceutical agents that can reverse this effect should be helpful in treating depressed patients. Therefore, the primary targets of various antidepressant medications are serotonin transports of the brain. Since serotonin is activated when released by neurons into the synapse, antidepressants function at the synapse to enhance serotonin activity. Normally, serotonin's actions in the synapse are terminated by its being taken back into the neuron then releases it at which point "it is either recycled for reuse as a transmitter or broken down into its metabolic by products and transported out of the brain." As a result, antidepressants work to increase serotonin levels at the synapse by blocking serotonin reuptake (2).

The newest medications used to suppress depression are collectively known as selective serotonin inhibitors (SSRIs). These drugs work by altering the function of neurons that release serotonin by blocking the reuptake of serotonin back into the cell. Therefore the level of serotonin activity is increased in any part of the nervous system that uses this neurotransmitter as a chemical signal between cells. The SSRIs have developed into the drugof choice because they render fewer side effects due to their limited action to reuptake serotonin alone and no other neurotransmitters. Fluoxetine, commonly known as Prozac, has become so widespread that it is not only used to treat depression, but also used for people that lack self-esteem, fear rejection, and lack the ability to experience pleasure. Unfortunately, although these SSRIs are effective in treating depression and are the least toxic of the antidepressants, they do produce some harmful side effects. In fact, some have defined the presence of certain side effects due to SSRIs as "serotonin syndrome"(2).

The serotonin syndrome is generally caused by a combination of two or more drugs, one of which is often a selective serotonergic medication. The drugs which we know most frequently contribute to this condition are the combining of MAOIs with Prozac or other drugs that have a powerful effect upon serotonin. The combination of lithium with these selective serotonergic agents has been implicated in enhancing the serotonin syndrome. The tricyclic antidepressants, lithium, MAOIs, SSRIs, ECT (electric shock treatment), tryptophan, and the serotonin agonists (fenfluramine) all enhance serotonin neurotransmission and can contribute to this syndrome. Anything that will raise the level of serotonin can bring on this hyperserotonergic condition. The optimal treatment for the serotonin syndrome is discontinuation of the offending medication is discontinued, the condition will often resolve on its own within a 24 hour period. If the medication is not discontinued the condition can progress rapidly to a more serious state and become fatal. It should be apparent that the greater the enhancement of serotonin levels, the greater the chances of producing the serotonin syndrome (3).

Because of the effects of the serotonin syndrome, researchers have found a better way to raise serotonin levels. 5-Hydroxytryptophan (5-HTP) may be useful for a wide range of health problems derived from a lack of brain serotonin. Problems such as insomnia, depression, obesity, eating disorders, PMS, panic attacks, alcoholism, anxiety disorders, and bulimia. 5-HTP itself does not do this. 5-HTP is a precursor to the neurotransmitter serotonin. 5-HTP has been used as a natural replacement for prescription antidepressants. It has been used effectively in research for weight loss, depression, anxiety, nerves, headaches, appetite suppressive and ADD. This vitamin has become the replacement for prescription medications such as Prozac or Zoloft and is known to raise brain serotonin levels naturally (4). Recent studies show that 5-HTP works in relation to St. John's Wort and SSRIs like Prozac. In one particular study of patients taking 5-HTP and patients taking SSRI, there was a 50% improvement with 5-HTP proving to be better tolerated than the SSRI and having about a 11% lower failure rate than the SSRI group (5).

According to other researchers, an even better way to raise serotonin levels would be to get daily exercise. The most effective way of raising the serotonin level is with vigorous exercise. Studies have shown that serotonin levels are raised with increased activity and the production of serotonin is increased for some days after the activity. This is the safest way of increasing the serotonin level and there are numerous benefits to be gained by regular exercise (6). In observing these findings, there is a basic understanding of serotonin and its functions. Serotonin is recognized as a very important neurotransmitter that has a profound effect on many aspects of behavior. Extensive research has been done, and is being continued, on the complex mechanisms by which serotonin operates. The most useful outcome of such studies is the introduction of pharmaceutical agents into the medical community. New studies are conducted everyday to learn more about the exact nature of serotonin and its widespread use throughout the human body(2).

Future serotonin research should continue to deal with the discovery of serotonin receptors and their functions, however there are not enough studies geared toward the comparison of 5-HTP and SSRIs. Since the distinction between 5-HTP and SSRIs has been made, and 5-HTP is known to be a better treatment to lower levels of serotonin there needs to be more research in this area. With more studies on 5-HTP, medical professionals may find new alternatives to the treatment of low serotonin levels. This could possibly reduce the serotonin syndrome among patients and lead to better treatments overall.

The idea of getting daily exercise to boast serotonin levels is a great discovery that needs to be discussed further. More studies should be conducted to show how daily exercise, along with a good diet, can help raise serotonin levels. Such research may lead to patients learning how to treat themselves without relying on any type of prescription drugs. This may also lead to a decrease in the experience of serotonin syndrome.

WWW Sources

1) Serotonin: The Neurotransmitter for the 90's

2) Widespread Uses of Serotonin

3) The Serotonin Syndrome

4)5-Hyroxytryptophan

5)5-HTP, Prozac Alternative

6) Getting High on Serotonin - Neurotransmitters and Health




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