Common monoamines used by nerves are norepinephrine, dopamine, and serotonin. Neurons produce the first two by making slight modifications to the amino acid tyrosine using a set of specific enzymes.
When chemicals are used to take a message across a synapse, the chemicals are called neurotransmitters. Thus, the monoamines are examples of neurotransmitters. Besides monoamines, the nervous system employs several amino acids for this job. The most important are glutamic acid (also called glutamate), GABA, and glycine. GABA, derived by enzyme action upon glutamic acid, has been implicated in the anti-anxiety effects of alcohol and the class of tranquilizers called benzodiazepines. This group includes Valium, Librium, Xanax, and Ativan.
In technical language, the monomamine hypothesis argues that depression is caused by insufficient activity of monoaminergic neurons. Most research points to serotonin and norepinephrine as the chief monoamines involved in depression. All the main treatments for depression increase the amount of these neurotransmitters in synapses. Some researches believe that dopamine is also associated with mood disorders. Dopamine is also considered the chief chemical in addiction--that is the elation part of addiction. Our brain gives us good feelings when dopamine is released by neurons in a small, special area of the brain named the nucleus accumbens. Our brains grant us pleasure to make us continue doing activities, such as eating and having sex, that allow our species to survive. Drugs like alcohol, morphine, heroin, cocaine, nicotine, and amphetamine stimulate the release of dopamine in the nucleus accumbens.
In this illustration a nerve impulse travels from the left in the presynaptic neuron. Neurotransmitters are released--actually thousands of them. The neurotransmitters diffuse "or drift" over to the receptors--there are many more receptors then are shown.
Presynaptic neuron is the neuron that releases neurotransmitters into synapse when a nerve impulse arrives. It begins with the prefix "pre" which means before just as "predict" means to tell before.
Postsynaptic neuron is the neuron that receives neurotransmitters from the presynaptic neuron. "Post" means after. For example "postmortem" means after death.
Receptors are rather large proteins that receive neurotransmitters like serotonin. Receptors sit on the plasma membrane, the outer boundary of the cell. The receptor has parts that stick out, parts that float in the membrane, and still other parts that reach into the cell.
Receptors are folded in a way to form a pocket that the neurotransmitter can stick or bind to. The binding process is similar to magnets sticking to a refrigerator door; magnets will attach to the door, but not to a wall, a window, or to curtains. Once the neurotransmitter binds to a receptor, the receptor changes shape in a way that takes the message into the cell. The message can then cause changes inside the neuron.
A group of chemicals cooperate to spread a message through the cell. G-protein-coupled receptors are the kind used by the monoamines associated with depression. These receptors are attached or "coupled" to G-proteins, so-called because they bind with chemicals called guanine nucleotides (GDP and GTP. G-proteins have three parts or subunits named after the first three letters of the Greek alphabet--alpha, beta, gamma. Usually, the G-protein bears an attached GDP. When a chemical like serotonin binds to the receptor on the receptor (outside the cell) the receptors shape changes inside the cell. This shape change flips on the G-protein. As a result, GTP replaces the GDP, the beta and gamma subunits split off, and the G-protein moves over to the enzyme adenylate cyclase and turns it on. Adenylate cyclase then produces lots of a phosphate chemical called cyclic AMP(cAMP) from ATP. The cAMP can then go far and wide to spread the message to other parts of the cell. Sometimes protein kinase is involved. Eventually, the message might go to the nucleus and turn on a gene to make some special chemicals. Note, the "ase" ending in kinase and cyclase means the substance is an enzyme. A number of recent reports have shown bipolar individuals to have increased G Protein and protein kinase concentrations.
To summarize in scientific language, when neurotransmitters such as norepinephrine or serotonin cross a synapse and bind with a receptor, the receptor relays a signal through several proteins resulting in the possible activation of a gene. At times the nerve is made more sensitive or is inhibited that is it is more likely or less likely to send other messages onward to other neurons. Norepinephrine, serotonin, and dopamine often inhibit the postsynaptic neuron. That is they shut down the spread of a message. How can stopping messages make one feel better during depression? Remember, earlier I said a lack of transmitter activity causes depression. Yet when we increase this activity with an antidepressant, the second neuron (the Postsynaptic cell) is frequently inhibited from sending messages. In depression, one might think that the nerves need stimulation, the more the better. However, based on the studies of what antidepressants do, less stimulation relieves symptoms. The key may be that only certain brain areas are slowed down, not the entire brain. People prone to depression have certain attitudes and beliefs. They are afraid of making mistakes. They are perfectionists. Maybe their need to be perfect is turned off as an effect of the inhibition caused by the rise in serotonin activity. Maybe their guilt machine is shut down. Besides using medicines, depression is successfully treated with cognitive therapy which aims to change the depressive's ingrained thought patterns. So, it seems, that one can train the mind to think differently or take a pill to change its thinking.
A second hypothesis of action involves a reduction in the number of receptors on the Postsynaptic neurons; this process (called subsensitivity) occurs with all treatments and takes 2-3 weeks--the same amount of time required to raise a patient's mood.
Still other theories are being considered. Almost all experts agree that we do not really understand what is going on during depression and that the mechanism is probably quite complicated. Recent work suggests that some people may be genetically predisposed to depression because the serotonin transporters (part that carries out reuptake) malfunctions when a person is subjected to stress--otherwise it works OK.
Corticotropin releasing hormone CRH) is believed to be involved in depression. The amygdale (Greek word for almond), an almond shaped structure, reacts to fear-evoking stimuli by giving off CRH in the part of the brain controlling the autonomic nervous system which includes the system controlling the famous "fight or flight" response.
Common Neurotransmitters
| Abbreviation | Metabolite(s) | |
| Serotonin | 5-HT | 5-HIAA |
| Norepinephrine | NE | MHPG, VMA |
| Dopamine | DA | DOPAC, HVA |
Researchers measure the levels of the transmitters and their metabolites--that is the chemical they are changed into after being used. For example, the metabolites from the food of most breathing organisms are carbon dioxide and water. By breathing on a cold window, one can see the water in one's breath. The level of the neurotransmitter may not vary much, but a rise in the metabolites means activity has increased. For example, since our blood sugar level stays within a certain range in most healthy people one might think that little sugar is being used. However, our constant exhaling of carbon dioxide and water shows that we are burning a lot of sugar for energy.
Some of the references used for this article are as follows:
Brown, A. and S. Gerson. 1993. "Dopamine and depression." J. Neural Transmission. 91: 75-109.
Carlson, N. 1991. Physiology of Behavior. Allyn and Bacon. Boston.
Hariri, A., V. Mattay, A. Tessitore, B. Kolachana, F. Fera, D. Goldman, M. Egan, and D. Weinberger. 2002. "Serotonin Transporter Genetic Variation and the Response of the Human Amygdala." Science 297: 400-403.
http://users.rcn.com/jkimball.ma.ultranet/Biology Pages/
Sapolsky, R. 2003. "Taming Stress." Scientific American. 289(3) 87-95
Williams, R. I. Ferrier, and A. Young. 1998. "Mood and neuropsychological function in depression: the role of corticosteroids and serotonin." Psychological Medicine. 28: 573-584.
Willner, P. 2000. "Dopaminergic Mechanisms in Depression and Mania."http://www.acnp.org/g4/GN401000093/CH.html