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What is Dopamine and How Does it Affect Your Health?

Dopamine is a fascinating and incredibly complex neurotransmitter (a naturally occurring chemical that carries information from one neuron to another) that plays a vital role in many aspects of our physical, mental/emotional, and spiritual health. It is an ancient molecule and exists in every animal species from the lizard to human beings. However, we homo sapiens have more dopamine than others.

Dopamine Molecule

It is the predominant neurotransmitter in your prefrontal cortex, (divided into the lateral, orbitofrontal and medial prefrontal areas) which is where cognitive behavior is processed, personality is expressed, orchestration of thoughts and actions in accordance with internal goals occurs, and executive function resides. Executive function pertains to making decisions, differentiating between good and bad, better or best, the same and different, conflicting thoughts, working towards goals, determining consequences of current actions and predicting outcomes, and suppressing urges that could lead to outcomes that are illegal or socially unacceptable. This is the area of the brain that houses the headquarters for your personality. How well your prefrontal cortex functions is highly dependent on your levels of dopamine. Dopamine is unique in that it may be inhibitory (calm the brain) or excitatory (stimulate the brain).

As is the case with all neurotransmitters, dopamine needs to be present in just right the amount; too much or not enough and many problems can arise. Not enough dopamine is associated with certain types of mental retardation, alcoholism and addictions of all kinds, attention deficit, hyperactivity, poor impulse control, Alzheimer’s, Parkinson’s, binge eating, bulimia, depression, gambling, apathy, loss of motivation, aggression, adrenal fatigue and lack of energy. Dopamine is what enables us to feel pleasure, desire, joy, and connection to others, makes us motivated and energized, pay attention and focused, and is the driving force behind competitiveness and a sense of adventure and helps modulate stress. It is what drives us to take risks, compels us to move forward in life and elicits a sense of satiation after we complete a task and provides motivation to act. While too much dopamine can result in an overactive sexual desire, bipolar disorders (the manic aspect), autism, anxiety, schizophrenia, and psychosis. On the spiritual level, an imbalance in dopamine can be a major contributor to feeling disconnected and a loss of inner peace.

Dopamine Synthesis

Along with norepinephrine and epinephrine, dopamine is in a class of naturally occurring chemicals called catecholamines.

Catecholamine Synthesis

Like every neurotransmitter, dopamine is formed from the nutrients in our food. As you can see in the chart above, the amino acid phenylalanine is converted into another amino acid called Tyrosine with an enzyme called phenylalanine hydroxylase in conjunction with the cofactors of iron, niacin and tetrahydrobiopterin (BH4). Then Tyrposine is converted into another substance called L Dopa with the enzyme tyrosine hydroxylase and the cofactors of iron, niacin, folic acid, and tetrahydrobiopterin (BH4). Then L dopa is converted into dopamine with another enzyme called dopa decarboxylase and the cofactor P5P, which is the active form of vitamin B6. Tyrosine can cross the blood brain barrier, but dopamine cannot. Therefore, the dopamine needed for the brain can only be manufactured within the brain with these precursors (cofactors) and enzymes.

Dopamine can then be converted into norepinephrine with the enzyme called dopamine beta hydroxylase and the cofactors of copper and vitamin C. Then norepinephrine is converted into epinephrine through methylation and requires the enzyme called phenylethanolamine N-methyltransferase and the cofactors SAMe and magnesium.

Therefore, if you don’t have enough of these nutrients or enzymes, then the production process can be inhibited and dopamine may not be available in sufficient levels or in some cases it may build up in excess. For example, not enough iron and you can’t convert tyrosine to L dopa, which means there is no dopa to convert into dopamine. Not enough P5P (B6) and you can’t convert L Dopa into Dopamine. Alternatively, if you don’ t have adequate levels of copper or vitamin C, then dopamine can’t be converted into norepinephrine, in which case there will be excess dopamine. Since much of the population is eating a nutrient deficient diet, many people do not have enough of these nutrients to produce adequate dopamine and maintain balance, thus one of the primary reasons why our society is plagued with conditions like attention deficit, hyperactivity, depression, addiction, eating disorders, violence, Parkinson’s, etc.

The diet needs to provide the brain with adequate levels of these nutrients needed to produce dopamine each and every day and the diet that does this best is a diet that is rich in animal protein and fat, and moderate levels of low-starch vegetables, like that found in the Primal/Paleo diet. Additionally, there are many foods and substances like sugar, caffeine, chocolate, nicotine, alcohol, marijuana and all psychotropic drugs (both prescription and recreational), as well as complex carbohydrates like whole grains, potatoes, or any high starch food, and artificial sweeteners, that can deplete neurotransmitter levels. So, it is equally important to avoid these substances as well in order to support healthy neurotransmitter production and function.

There are a variety of genetic polymorphisms that one may be born with that can inhibit the enzymes needed in this process as well, depending on which enzymes are absent or deficient, dopamine may be deficient or in excess. For example, some people may be deficient in tyrosine hydroxylase, which is needed to convert tyrosine into L Dopa and can result in movement disorders or a wide variety of neurological problems. One may also be born with a deficiency in phenylalanine hydroxylase, which results in excess levels of phenylalanine and a very serious disorder called phenylketonuria or PKU. There can also be deficiencies in dopa decarboxylase, which also results in movement disorders, abnormal eye movements, and impairment of the autonomic nervous system and other neurological disruptions.  A deficiency in dopamine beta hydroxylase is very rare, but has serious consequences on the autonomic nervous system.

The enzyme dopamine beta hydroxylase can also be inhibited by the presence of a class of bacteria called clostridia. There are a variety of different species within this class; the tetanus bacteria and clostridium difficile are two of the most well known. Dr. William Shaw explains that this “results in an excess of dopamine and a deficit in norepinephrine, leading to obsessive, compulsive, stereotypical symptoms associated with dopamine and reduced exploratory behavior and learning in novel environments” associated with a norepinephrine deficit commonly seen in autistic children. These disorder, as well as schizophrenia and psychoses, often respond favorably to treatment with the antibiotic vancomycin, which targets clostridia.

Tetrahydrobiopterin (BH4) is another naturally occurring substance used as a cofactor with phenylalanine hydroxylase and tyrosine hydroxylase in the conversion of phenylalanine into tyrosine and tyrosine into L dopa. There are a variety of genetic mutations that may result in a deficiency of tetrahydrobiopterin (BH4) which can impede conversion, and result in a build up of phenylalanine, also contributing to PKU.

Methylation, which is the conversion of one substance into another is needed for many aspects of neurotransmitter production and function, including dopamine. A variety of nutrients are needed for the methylation process including folic acid, B12, B6, magnesium, and SAMe. If one is deficient in any of these nutrients, then methylation may be impaired. Additionally, there are a variety of genetic polymorphisms that can impair methylation as well, like the COMT gene and MTHFr gene. The COMT gene encodes for the production of the COMT enzyme, which is needed to deactivate dopamine. A problem with the COMT gene will result in less COMT enzyme, which results in an excess of dopamine. On the other hand, when activity of the COMT enzyme is decreased less dopamine is deactivated and less methyl groups are used in the process, which means you want to lower methyl group production and supplementation that would affect it. Too much supplementation for methyl groups when there is a problem with a COMT enzyme can lead to mood swings, depression, hyperactivity, stims, and more and is also a burden on the adrenal glands. Lithium is needed for the uptake of B12 and folic acid in order to form the methyl groups needed for methylation and is believed to increase production of the COMT enzyme as well.

Therefore, if one is not methylating properly, which is the case for many people in the population, there can be problems with dopamine insufficiency or excess. For example, as demonstrated above, dopamine is converted into norepinephrine and then it should be converted into epinephrine. Methylation is needed to convert the norepinephrine into epinephrine and the COMT gene is involved in this process as well, and if that doesn’t happen then norepinephrine builds up in excess in the brain. Excess norepinephrine is toxic to the brain, it results in a wide array of symptoms like anxiety, panic attacks, fear, aggression, insomnia, restlessness, irritability to name a few.

Methylation is also very critical for the Dopamine D4 receptor, which is responsible for attention, focus and learning. The D4 receptor operates by inverting into the cell and coming back out again and needs a very flexible cell to perform this function. Methylation is needed for this flexibility, therefore if methylation is not occurring, inversion won’t take place and the cell cannot use the dopamine that is present efficiently. This D4 receptor methylation activity is influenced by the availability of 5 MTHF, (5 methyl tetrahydrofolate), the active form of folate. If there is not enough of 5 MTHF present, then dopamine receptors will not be activated even if there are high levels of dopamine present. First of all there needs to be sufficient levels of folate in your food. However, many people cannot convert folate into the necessary 5 MTHF because of a genetic polymorphism in the enzyme that is needed to make this conversion called MTHFr (methyl tetrahydrofoalte reductase enzyme). When that is the case, supplementation with methyl tetrahydrofoalte and other nutrients needed for the methylation cycle may be helpful. MTHFr is also needed for homocysteine to convert into methionine.

So even if one has adequate dopamine production, they can experience deficiency symptoms if they aren’t methylating properly. There is testing that can be done to identify whether one has genetic problems with the COMT or MTHFr genes, which can be acquired through me. Contact me to set up a phone consultation, if you are interested.

One may be born with an overactive basal ganglia, in which case they may be edgy and anxious throughout childhood. The individual with excess dopamine may feel like a deer in headlights when they have to do something like present a paper in front of their class. Trauma (childhood abuse, neglect, natural disaster, etc.) during childhood can cause the basal ganglia to become overactive, in which case it leads to anxiety and PTSD.

Candida Overgrowth and Dopamine

If one has Candida overgrowth, one of the toxins produced by Candida called acetaldehyde, has the uncanny ability of combining with two key neurotransmitters in the brain, serotonin and dopamine, and form substances called tetrahydroisoquinolines, which closely resemble opiates in structure, function and potential for addiction, thereby producing an opiate-like high. This may generate cravings for addictive substances of all kinds including sugar and carbs, alcohol or even opiates and lead to opioid addiction or in the case of the individual trying to recover from addiction to sugar and carbs or drugs and alcohol, it may result in relapse. Since these substance are interacting with our neurons that produce our natural opiates called endorphins, this can eventually lead to endorphin deficiency. Endorphins are another critical neurotransmitter for modifying emotional and physical pain, providing us with feelings of empowerment, self-esteem, self confidence, joy, ability to relax, and well-being.  Additionally, when acetaldehyde interacts with dopamine, one of the tetrahydroisoquinolines, it is converted into a neurotoxin called salsolinol, that then kills off brain cells that contain dopamine, resulting in a deficiency in dopamine. Recent research suggests that the killing off of dopamine by Candida may be an underlying cause of Parkinson’s.

Stress and Dopamine

High levels of stress can also deplete dopamine levels, as well as many other important neurotransmitters. Like GABA, endorphins, and serotonin, dopamine is called upon to help the body cope when we are under stress. If stress levels are high and never ending, then dopamine will be consistently drained to deal with the stress at hand. If there is not enough dopamine to begin with because of a poor diet, environmental toxins, or a genetic polymorphism, then a vicious cycle ensues. Because the lack of dopamine to help manage the stress creates even more stress and this puts a heavy burden on the adrenal glands. This is a significant factor in many health conditions like adrenal fatigue; adrenal fatigue can drain your dopamine levels, while at the same time insufficient levels of dopamine can perpetuate adrenal fatigue. On the other hand, excess dopamine can also cause significant stress, impair the autonomic nervous system and also contribute to adrenal fatigue.

Additionally, when we are under stress, our norepinephrine is elevated. This can cause a backlog in the conversion of dopamine to norepinephrine process, leading to elevated levels of dopamine activity.

Toxins and Dopamine

Toxins of all kinds like pesticides, herbicides, heavy metals, petrochemicals and those found in conventional cleaning supplies, air fresheners, personal care products, cosmetics, laundry soap, dish soap, colognes and perfumes or within one’s own body produced by microbes like Candida, parasites and bacteria, can all impair production or function of dopamine and other neurotransmitters. Furthermore, eliminating toxins from the body requires a high level of nutrients. The more toxins you are exposed to the more nutrients that are needed. This can take away from the nutrients that are needed to produce neurotransmitters. Not only that, toxins are a form of stress on the body, that sets off the stress response system, which as we already established means a lot of dopamine will be used up to deal with the stress at hand. Therefore, living an environmental friendly lifestyle that reduces the presence of toxins in your living environment is critical for maintaining adequate dopamine levels.

Serotonin’s Impact on Dopamine

Serotonin, another awesome neurotransmitter, plays a vital role in neurodevelopment, neurogenesis and neural migration. Studies on mice have demonstrated that when brains are forming in the womb, the serotonin of the mother helps “direct neurons to the right place at the right time.” If the mother is deficient in serotonin, her offspring are deficient in dopamine and exhibit the classic low dopamine symptoms of inattention and poor impulse control. A study on humans demonstrated this seems to be the case for us as well, mother’s without adequate serotonin bear a very high number of children with ADHD father’s do as well, but not as much as mothers. The parents in this study had a variety of genetic mutations in TH1 (tryptophan hydroxylase 1), an enzyme needed to help coat the baby’s brain with serotonin. Therefore, ensuring you have adequate levels of serotonin is essential for dopamine balance.

Histamine and Dopamine

Another neurotransmitter called histamine is important for regulating the release of serotonin, dopamine and norepinephrine. It counterbalances dopamine levels. Therefore, if histamine is low, it can increase dopamine levels; or if it is high, it can lead to low levels of dopamine.

Dopamine Pathways

Dopamine is released when dopamine neurons are stimulated. The effects produced by the dopamine being released will vary depending on what area of the brain it is released from, what type of neuron is receiving it and where they are going, the type of receptor that is binding to the dopamine, and the role that is played by both the releasing and receiving neurons.

Although the brain has about 200 billion neurons only about 20,000 of them are for dopamine, which are distributed in four primary pathways. Dopamine is manufactured in two areas of the brain called the substantial nigra and the ventral segmental area, and then reaches out to other areas from this starting point.

The nigrostriatal tract carries dopamine from the substantial nigra to the striatum or basal ganglia. Neurons in this area are in charge of motor control in the body. Loss of dopaminergic neurons in the substantial nigra results in tremors, stiffness, and loss of voluntary movement as exhibited in Parkinson’s disease and various chorea diseases.

The mesolimbic pathway travels from the ventral tegmental area to the limbic system, both are primitive parts of the brain associated with survival. Activities or substances that produce pleasure activate the VTA. This pathway includes the hippocampus, amygdala, locus ceruleus, and medial frontal cortex. It governs reward, emotion, motivation and pleasure and is also known as the reward pathway or pleasure pathway. This pathway is involved with addiction and psychosis.

The primary role of the mesolimbic pathway is to “reward” us when we engage in certain behaviors that are essential for our survival like eating food, drinking water, nurturing, and procreation and ensure that we will repeat these behaviors in the future, so our species can survive. When dopamine is released in this area of the brain, it produces a mild euphoria, joy, desire, and pleasure; improves mood, alertness, and libido; and creates a heightened sense of well-being. This is our “reward.” Basically dopamine reinforces behavior that is needed for our survival by making us feel good.

A small amount of dopamine in the VTA travels to another area of the brain known as the nucleus accumbens, in response to sex, eating, drinking water, falling in love, giving or receiving nurturing as well as a variety of other activities like communing with nature, listening to music, or anything that produces pleasurable feelings. However, this pathway is also activated and dopamine will be released in very high amounts in response to sugar, grains and any other high carb food, alcohol, nicotine, caffeine, and all mind-altering drugs like cocaine, marijuana, amphetamines, heroin, etc., as well as video games, gambling, and even Facebook. The volume of dopamine sent out in response to alcohol and drugs of abuse is much higher, (two to ten times higher) than the volume that will be generated by natural means like eating and its effects last significantly longer. MRI Studies have found that Facebook, twitter and other social media is just as harmful and addictive as cocaine and methamphetamine, because it overstimulates your brain in the same manner.

When this area of the brain gets flooded with dopamine, it creates the intense euphoria that is known as “getting or being high”. Serotonin in the nucleus accumbens, which is responsible for feelings of satiation and inhibition gets suppressed simultaneously. The amygdala interprets whether this a positive or negative event and the hippocampus which is our memory center will store the information in your memory bank that a particular substance or behavior will produce the reward. The prefrontal cortex will get involved as well with planning and motivation.

Dopamine starts to fill the nucleus accumbens as soon as you see the object or substance that you have learned will produce a reward. For example, when you see a commercial on TV for a candy bar, a glass of beer or a piece of pizza, and you feel like running out to get one of them, dopamine is responsible for that behavior. If you don’t act on it and the expected reward does not occur, then dopamine levels drop and the locus ceruleus which is loaded with norepinephrine, sets off an alarm which drives you to go after the reward at all cost. The bigger the surge in dopamine that is produced the more pleasure one will experience and the more one will be driven to repeat the behavior. This process of events is what creates the addiction cycle.

If one continues to use drugs and alcohol, the brain will respond to these surges in dopamine levels by reducing the number of dopamine receptors at the synapse and the remaining receptors become less sensitive to dopamine, which means it will now require more of the mind altering substance or activity to achieve the same result. This is called tolerance. The longer one uses the drug or activity, then the more desensitized the receptors become. Less dopamine receptors in this area means less dopamine, which means one will experience loss of motivation, joy, happiness, and pleasure. Tolerance will continue to build and more and more of the drug will be needed to get high. Eventually, dopamine levels are so low that the brain becomes completely dependent on the drug or activity of choice to stimulate the effects of dopamine – addicted. Since serotonin is suppressed, then one will also experience symptoms of low serotonin like compulsive overeating and depression.

The nucleus accumbens is also rich in GABA neurons, but that is a discussion for another day and the VTA is also rich in serotonin and influenced by endorphins another important neurotransmitter that is stimulated by drugs like heroin and morphine.

On the other hand, high levels of dopamine are also found in this area of the brain in people with post-traumatic stress disorder, and is partly responsible for the paranoia and heightened vigilance that accompanies this condition.

This area of the brain is also associated with risk taking. Studies have found that people who have freer flowing dopamine are more likely to push the limits and take higher risks. The higher the risk the bigger the release of dopamine. Of course this is a good thing or otherwise we’d never take any risks or accomplish anything, and life as we know it would not even exist. However, if dopamine is too high or there is a problem with receptors in this area, then one may take risks that puts their life in danger.

We are all hard-wired to enjoy the thrill of the hunt, because hunting used to be essential for our survival. The hunt can take place in many ways, like grocery shopping, shopping for any item what so ever, searching the Internet for Information, looking for a partner, exploring new territory, going on an adventure, etc. Studies actually demonstrate that we get quite a significant surge in dopamine when we are hunting for something new.

The risk taker is not the same as an adrenaline junkie or a thrill seeker. The thrill seeker or adrenaline junkie is seeking the reward experienced from adrenalin, which is released when we are in a life threatening situation and may also be triggered by horror movies. The risk taker, explorer, adventurer, or people who start their own business, go after what they want, climb mountains, trek into unknown territory, and run for President, etc., are driven by dopamine to achieve, explore and be adventurous. Although, it is possible that one may become addicted to both the risk taking and the adrenaline rush.

In a fascinating study in the UK we discovered that dopamine is also activated by aversive events, but in a different subsection of the VTA. In response to happy events, an area called the dorsal VTA is activated. When exposed to an aversive event, dopamine in the dorsal VTA is inhibited or doesn’t’ respond at all. However in another subsection called the ventral VTA, there is a very high level of activation. Then when the aversive event is over, there is a release of dopamine in the dorsal VTA. So why would this be so? Because learning to stay away from something aversive that may threaten our survival is necessary and achieving relief from the aversive event would be our reward. We are rewarded with dopamine when the aversive event is over to teach us that we should avoid this type of situation.

The mesocortical pathway brings dopamine from the ventral tegmental area to the dorsolateral frontal cortex. This area of the brain is at the helm of motivation, responsibility, planning, prioritizing, and emotional response to some degree. Problems here are associated with ADHD and depression.

The tuberoinfundibulnar pathway is between the hypothalamus and the pituitary. One of the most important functions of this pathway is to regulate prolactin, a substance that is needed to stimulate lactation. Dopamine inhibits the release of prolactin, so in order for lactation to occur, dopamine must be blocked. When dopamine is in use for this purpose it is considered a neurohormone, rather than a neurotransmitter.

Outside the brain, dopamine is connected with nausea and heart and kidney function.

Types of Dopamine Receptors

Currently, there are five known dopamine receptors, but it is believed there are others that have not yet been discovered. They are known as D1, D2, D3, D4, and D5 and each one sends a different signal. They are classified into two different families based on certain properties called D1-like and D2-like.

D1 is the most abundant dopamine receptor in the central nervous system and is part of the D1-like family. They are expressed at a high level of density in the striatum, mesolimbic, nigrostriatal, and mesocortical areas, nucleus accumbens, substantial nigra, frontal cortex, and the amygdala, and at less density in cerebellum, thalamic and hypothalamic areas, and the hippocampus. When dopamine binds with D1 receptors it plays a part in some behavioral responses, manages the growth and development of neurons in the brain, and modulates the actions of the D2 dopamine receptor and play a role in the cardiovascular system.

Dopamine receptor D2 is found in numerous places within the brain, but the highest concentrations are located in the nucleus accumbens, striatum and olfactory tubercle. Significant concentrations are also expressed in the VTA, substantia nigra, septum, cortical areas, hypothalamus, amygdala and hippocampus. D2, in combination with D1, is the receptor that is involved with addictions of all kinds, bipolar disorder and psychoses. Genetic mutations may occur with D2 that have been connected with the movement disorder myoclonus dystonia and schizophrenia. It is a member of the D2-like family.

The D3 dopamine receptor is expressed the most in areas of the limbic system known as the islands of Calleja, the nucleus accumbens and the olfactory tubercle, but at significantly lower levels in the VTA, striatum, substantia nigra pas compacta, septal area, various cortical areas and the hippocampus. It is a member of the D2-like family. Both islands of Calleja and the nucleus accumbens are involved with reward, pleasure and addiction, as well as a variety of types of emotions like laughter. Genetic mutations occur in this receptor that make one more susceptible to a movement disorder called essential tremor 1.

Dopamine receptor D4 is a member of the D2-like family and is associated with exploratory behavior, risk taking, cognitive functions, learning, focus, attention, and motor coordination and involved with conditions like ADHD, Parkinson’s and schizophrenia. Genetic mutations in this receptor have been shown to be connected to a wide variety of behavioral issues like attention deficit hyperactivity disorder, a novelty or sensation seeking personality type, individuals addicted to opiates, and autonomic nervous system dysfunction. It is expressed in lower levels than other receptors in the brain in the hypothalamus, amygdala, hippocampus, frontal cortex, thalamus, globus pallidus, and substantia nigra pars reticulate.

The D5 dopamine receptor is expressed in low density throughout many regions of the brain in all areas including the substantia nigra, hippocampus, amygdala, prefrontal cortex, cingulated cortex, entorhinal cortex, premotor cortex and dentate gyrus, and a really low expression in the nucleus accumbens and caudate nucleus. It is a member of the D1-like family and is plays a role in numerous functions associated with behavior, emotion, long-term memory and smell. D5 receptors have a “10 fold higher affinity for dopamine” than D1 receptors, which means they bind with dopamine much more easily than D1.

D1 and D2 are both important for learning and memory that is mediated by the prefrontal cortex, while D1, D2 and D3 regulate locomotor activity and D3, D4, and D5 play a minor role in some aspects of cognitive functions mediated by hippocampal areas.

Outside the central nervous system dopamine receptors are involved with moderating other functions like vision, olfaction, kidneys (D1); aldosterone secretion and sympathetic nervous system tone (adrenal gland D2); renal function, blood pressure, vasodilation and gastrointestinal motility (D1, D2, D4); and some hormone regulation like prolactin secretion (pituitary D2).

Dopamine Agonists and Antagonists

Some drugs are known as dopamine agonists and others as dopamine antagonists. An agonist drug will bind to the dopamine receptors instead of dopamine and stimulate the receptor directly. In other words, they mimic dopamine. Dopamine agonists are commonly used in the treatment of Parkinson’s, due to their ability to stimulate dopamine receptors even if someone is lacking dopamine neurons. A dopamine antagonist on the other hand, will bind to the dopamine receptor but it will not stimulate them, which has the effect of blocking, prevention or reversing the actions of dopamine, by inhibiting dopamine’s ability to attach to the receptor. Dopamine antagonists are commonly used in the treatment of schizophrenia, psychoses, or other mental health conditions where there is an overactive dopamine system.

Drugs that act directly on the receptor rather than the neurotransmitter are called direct acting, while some drugs like cocaine and amphetamines act against the neurotransmitter itself, are called indirect. The latter produces its effects by altering the flow of neurotransmitters. Whether a drug acts directly or indirectly can produce vastly different results in the same condition. For example, in individuals with Parkinson’s they have lost neurons that contain dopamine, so to compensate for this loss the brain will generate more dopamine receptors on other neurons. An indirect agonist would not be very effective in this case, since their action is dependent on dopamine neurons being present, while a direct agonist would stimulate the dopamine receptors even though the dopamine neurons are missing, so it would be more beneficial.

All neurotransmitters are recycled and reused through a process called reuptake, where the neurotransmitter will be sent back to the releasing neuron and in the case of dopamine, an enzyme called monoamine oxidase (MAO) will break it down. However, if dopamine is taken back into the vessel for storage, then MOA can’t act upon it. Some drugs, like Reserpine, operate by preventing the reuptake of dopamine and other neurotransmitters, which keeps dopamine in the cell and exposes it to MAO, thus significantly lowering the levels of dopamine available. Other drugs, like Deprenyl can inhibit MAO, which means dopamine will not be broken down, thus increasing dopamine levels. Another type of MAO actually has a protective effect on dopamine, rather than breaking it down. It will break down other neurotransmitters to protect transmission of dopamine. Some drugs are used to inhibit this form of MAO to increase other neurotransmitters like serotonin. Other drugs like cocaine and amphetamines can increase the quantity of dopamine in the synapse and produce similar effects, but they do so in completely different ways. Cocaine prevents reuptake, by binding to proteins that transport dopamine. However, not only does it “bully dopamine out of the way, it will remain connected to the transport protein for a much longer period of time than dopamine, which creates an exceptionally high level of dopamine for a prolonged time, thus a longer period of intense euphoria. While amphetamines stimulate the release of more dopamine.

There are many complications that can arise with both agonists and antagonists. Antagonists can cause dopamine deficiency and high doses of agonists can cause psychoses. Therefore, it is my opinion that drugs should be avoided, even those designed to manipulate neurotransmitters for a positive effect. Anytime a receptor is stimulated artificially the brain responds by cutting back on natural production of neurotransmitters or making them less responsive, in either case drugs, only perpetuate the problem that one is trying to address.

Sensitization and Desensitization of Dopamine

Neurons can become sensitized or desensitized to dopamine in response to exposure to drugs.

Long-term exposure to dopamine antagonists will increase dopamine receptors because the nervous system will try to compensate for the loss of stimulation by increasing dopamine itself. In the same fashion, the receptors become more responsive to dopamine. In both cases, this is called sensitization.

If dopamine itself or dopamine agonists stimulate dopamine receptors repeatedly, this overstimulation will prompt the brain to decrease the number of dopamine receptors and the receptors that remain will be less responsive to dopamine. This action is referred to as desensitization.

Desensitization is also known as tolerance. Exposure to a drug results in less response than it did previously. Tolerance demonstrates the nervous system’s attempt to maintain homeostasis within the cell despite the changes in the degree of stimulation to the receptor, which is needed to maintain equilibrium within the body in the presence of the drugs.

As you can imagine, when sensitization or desensitization occurs in areas of the brain that govern aspects like emotion, cognition, and motivation, the consequences can be quite severe.

Although both sensitization and desensitization generally occur in response to long-term exposure to drugs, that is not always the case. Both sensitization and desensitization can take place after one single exposure to drug, within a matter of minutes.

Sensitization or desensitization may also occur in response to other things besides drugs. Anything that overstimulates neurotransmitters like childhood abuse, serving in combat, or other extreme forms of stress, a junk food diet, and some environmental toxins, may lead to desensitization.

As you can see, dopamine is down right awesome and mind blowing in its complexity and this discussion only touches the surface. There is much more that can be a said about its impact on our mental and physical health, but this gives you a basic overview of some of the most critical aspects. The bottom line is that ensuring that you have adequate and balanced levels of dopamine is critical for your health in numerous ways. It’s also important to note, that most of the concepts we have covered that apply to dopamine apply to other neurotransmitters as well.

References

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Briscoux Frederic, Chakraborty Subbhojit, et. al. Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli. PNAS March 24, 2009 vol. 106 no. 12 4894-4899.http://www.pnas.org/content/106/12/4894

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http://www.utexas.edu/research/asrec/dopamine.html

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http://www.psychologytoday.com/blog/evolutionary-psychiatry/201105/adhd-and-moms-serotonin-deficiency

Deans, Emily, M.D. Dopamine Primer. Psychology Today, May 13, 2011.

http://www.psychologytoday.com/blog/evolutionary-psychiatry/201105/dopamine-primer

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Dr. William Shaw. Inhibition of dopamine conversion to norepinephrine by Clostridia metabolites appears to be a (the) major cause of autism, schizophrenia, and other neuropsychiatric disorders.http://www.greatplainslaboratory.com/home/eng/articles/Interference%20in%20dopamine%20conversion%20to%20norepinephrine%20FINAL.pdf

Dr. William Shaw. Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia http://www.greatplainslaboratory.com/home/eng/hphpa.asp

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Epp LM, Mravec B. Chronic polysystemic candidiasis as a possible contributor to onset of idiopathic Parkinson’s disease. Bratisl Lek Listy. 2006;107(6-7):227-30. http://www.ncbi.nlm.nih.gov/pubmed/17051898

Intelegen, Inc. “Acetaldehyde: A Common and Potent Neurotoxin How to Prevent the Damaging Effects of Smoking, Alcohol Consumption, and Air Pollution.” http://intelegen.com/nutrients/prevent_the_damaging_effects_of_.htm

{ 9 comments… add one }

  • nicki banks September 20, 2015, 6:48 pm

    I found the information on what is doparmine and how does it effect your health very informative. it was the most clearly written thus understood information regarding this that I have found yet.
    thank you.

  • Admin - Cynthia Perkins October 27, 2015, 11:53 am

    You’re welcome, Nicki. Thank you.

    Best,

    Cynthia

  • Rory November 20, 2015, 7:12 am

    Hello Cynthia,
    Thank you for the informative research.
    My son is coming down what we all know is Turrets. He is 6 years old.
    I need to understand so that I can try to help him and somehow possibly heal him with time.
    I love my children so I’m always trying to help.
    A studious mother.
    Rory

  • Karen Robertson November 26, 2015, 3:24 pm

    What a fantastic lot of info. Thank you soooo much. It has been of immense help in a pretty diar situation with my 21 yr old son who has suffered with extreme anxiety and depression since he was 14. Cynthia, I’m desperately trying to decide which way to go in terms of addressing my sons neurotransmitters. In a copper deficiency how does one increase norepinephrine and epinephrine? Copper required for the cofactor dopamine beta hydroxylase enzyme. I can’t see how one can do this naturally and wondered if, as a last resort, a synthetic Anti depressant may be the only option?? I really would be most grateful for ANY input/guidance.

    With enormous thanks

    Karen
    (St Andrews, Scotland, United Kingdom)

  • Admin - Cynthia Perkins December 18, 2015, 8:43 pm

    You’re welcome Karen. Copper can be replenished with a copper supplement. No, as explained above, antidepressants only deplete the neurotransmitters even more.

    Best,

    Cynthia

  • Vin March 26, 2016, 1:43 am

    Hi Cynthia, great site – first time I’ve come across complete info on various topics vs simplistic explanations.
    You’ve mentioned that various anti-depressants or supps can make matters worse by depleting / downregulating, but what about the mao-i approach?

    Like deprenyl in your article, what are your thoughts on low doses for preserving dopamine/getting a little extra dopamine?

    I’ve also read that tribulus is a natural mao-b inhibitor due to harmine content – any opinions on this for increasing dopamine?

  • Admin - Cynthia Perkins April 25, 2016, 11:00 pm

    Hi Vin,

    Anytime a drug is used to manipulate neurotransmitters, it perpetuates the problem, as discussed above. Doesn’t matter which drug we are speaking of. They all have that affect.

    Best,

    Cynthia

  • Valerie July 10, 2017, 8:14 am

    Will the sensitization process involved with chronic use of risperdal eventually correct in careful titration off the drug?

  • Admin - Cynthia Perkins July 21, 2017, 3:08 pm

    Valerie,

    Possibly, if all other factors needed to restore balance to neurotransmitters are addressed. You should take a look at the following page.

    http://www.holistichelp.net/blog/balancing-neurotransmitters-checklist/

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