Dopamine, What Is It and Why It Is Important for Motivation, Happiness, and Digestion

Dopamine, What Is It and Why It Is Important for Motivation, Happiness, and Digestion

Most people associate happiness with serotonin and the use of anti-depressants, but serotonin is more of the neurotransmitter associated with mood stabilization and wakefulness. Though both neurotransmitters are associated with alertness, dopamine is one of the main hormones which makes us feel happy and motivated. However, when homeostasis of the hormone is disrupted anxiety, mania, apathy, and depression occur depending on the fluctuation of the neurotransmitter. We are exposed to a lot of dopamine manipulators in our modern life, from our Facebook addiction, excessive blue light exposure, gambling, to sadly epidemic narcotics abuse. So, what is dopamine? What does proper regulation of this neurotransmitter have to do with our health, and what can be done to return it to homeostasis when needed?

What is Dopamine?

Dopamine is an organic catechol of the catecholamine and phenethylamine families that is needed by our body for many different crucial functions. The neurotransmitter is an amine that is made from removing a carboxyl group from its precursor L-DOPA (which many people know is a popular medication for Parkison’s disease). L-DOPA is produced from the amino acid L-tyrosine from catalyzation by the rate-limiting enzyme tyrosine hydroxylase, using oxygen, iron, and tetrahydrobiopterin (BH4) as cofactors. L-DOPA is synthesized within the brain, nervous system, pancreas, and kidneys. L-phenylalanine has to be metabolized into L-tyrosine using tyrosine hydroxylase to become L-DOPA. For the proper production of L-DOPA, pyridoxal phosphate (vitamin B6) is required. Gut bacteria within our digestive tract also produce dopamine including Escherichia and Bacillus. Production of catecholamines from L-tyrosine including dopamine eventually traps the active-site iron in the Fe(III) state within the cytosol of the cell, inhibiting tyrosine hydroxylase. Inhibition of tyrosine hydroxylase for a time reduces catecholamine production, maintaining proper homeostasis. Eventually, more catecholamines are needed by the body, and the active sites open back up from a reduction in circulating catecholamine leading to the production of tyrosine hydroxylase, increasing catecholamine production.^{1 2 3}

Plants produce the neurotransmitter and many foods that we consume contain it. Ingesting dopamine from food does not increase the amount of dopamine within our brain, Ingested dopamine is metabolized into dopamine sulfate within the mesentery and enters the bloodstream where it is filtered but the kidney’s and is excreted. “Plasma dopamine sulfate derives mainly from sulfoconjugation of dopamine synthesized from L-DOPA in the gastrointestinal tract. Both dietary and endogenous determinants affect plasma dopamine sulfate. The findings suggest an enzymatic gut-blood barrier for detoxifying exogenous dopamine and delimiting autocrine/paracrine effects of endogenous dopamine generated in a “third catecholamine system.” ^{4 5}

The neurotransmitter cannot cross the blood-brain barrier (L-DOPA, however, can cross the blood-brain barrier) because of lack of a proper transporter, and it is not lipid soluble. What amount of the neurotransmitter that is needed by the brain must be produced within. Dopamine is also a precursor for the synthesis of the neurotransmitters norepinephrine and epinephrine. Dopamine is converted into norepinephrine by the enzyme dopamine β-hydroxylase that requires copper, oxygen, and ascorbic acid to be produced. Norepinephrine is converted into epinephrine by the enzyme phenylethanolamine N-methyltransferase with S-adenosyl-L-methionine as the cofactor. Dopamine is broken down into homovanillic acid and catabolized by three enzymes, monoamine oxidase, catechol-O-methyl transferase, and aldehyde dehydrogenase to be eliminated by the kidneys in urine. Any polymorphisms in the genes that code these enzymes (which cause a deficiency in those enzymes) can lead to improper homeostasis.^{6 7 8}

Dopamine is synthesized and metabolized cellularly within the cytosol and is extremely susceptible to oxidation, especially in the presence of free iron. Oxidized dopamine can be inhibited cellularly by glutathione before it creates excessive oxidative stress and the formation of dopamine quinones. Dopamine oxidation leads to the formation of both reactive oxygen species and dopamine quinones, namely, 3,4-dopamine quinone, aminochrome, and indole-5,6-quinone. Dopamine quinones are very reactive and create oxidative stress within our mitochondria leading to poor health.^{9 10}

What Does Dopamine Do for Our Health?

Dopamine is the primary neurotransmitter that is associated with pleasure. Dopamine is one of the neurotransmitters that make us feel the emotion of happiness. Recent research has shown that dopamine has less to do with happiness and more to do with motivation and attentiveness. Our brain contains a dopamine reward pathway, which motivates us to be successful and obtain happiness. The brain produces dopamine when we obtain a reward that benefits us or people important to us. Primary rewards, which are rewards that are necessary for survival are sexual contact, liquids if we are thirsty, food if we are hungry, and positive parental care (including lactation) increase dopamine. Secondary rewards, which are rewards that are not inherently pleasurable or are not needed for survival can also increase dopamine, including winning the lottery, drug use like opioids, or your favorite sports team winning. Many people are aware that secondary rewards can lead to addiction including gambling or drug use, but primary rewards can as well, sex addiction and overeating.¹¹

Other than our reward pathway, dopamine:^{12 13 14 15 16 17}

• Inhibits norepinephrine release within blood vessels acting as a vasodilator.
• Regulates motor control of our muscles. Essential for motor function and the learning of new motor skills.
• Reduces sodium excretion and urine output.
• Reduces the activity of lymphocytes in the immune system.
• Enhances the activity of cones within the retina during the daytime while suppressing rods, increasing sensitivity to color and contrast.
• Inhibits secretion of the hormone prolactin by the pituitary gland. Neurons produce dopamine in the arcuate nucleus within the hypothalamus is secreted into the hypophyseal portal system of the median eminence, which supplies the pituitary gland and inhibits prolactin.
• Dopamine triggers nausea and vomiting by activating the dopamine receptors in the chemoreceptor trigger zone of the medulla oblongata.
• Dopamine is released into the small intestine by the pancreas and is released into the intestinal tract by dopamine-producing cells which may improve the integrity of our gastrointestinal mucosa and decrease intestinal motility (MMC) to help regulation when needed.

The body should tightly regulate dopamine production and utilization so we can maintain a healthy life. However, in our modern world, our environment causes sharp dopamine fluctuations. Excessive blue light exposure from our increased use of artificial lighting and constant need for screen time is having a drastic effect on our dopamine levels. One of the main triggers for dopamine production is retinal blue light exposure through the interaction of ultraviolet light and tyrosine. “Dopamine is a well-known modulator of circadian rhythms in the retina. In particular, the circadian release of vertebrate retinal DA (either endogenously expressed in the interplexiform, amacrine, or both cells, depending on the species) allows for proper light adaptation and transmission of light information to the SCN, via the melanopsin-expressing ipRGCs.” Light exposure and circadian rhythm genes also regulate the enzyme tyrosine hydroxylase. Dopamine production is strongly regulated by circadian rhythm and natural daytime light exposure. Increased artificial light exposure in our modern lives, especially at night is creating excessive amounts of dopamine and in doing so dramatically increases dopamine oxidation.^{18 19}

Some studies link proper natural light exposure and a decrease in the risk of developing Parkinson’s disease and depression. Seasonal effective disorder (depression that differs from the seasons, increases in the fall and winter) has been linked to a lack of natural light exposure during the fall and winter. Most people link it to a reduction of serotonin and depression. However, some studies that link it to a reduction of dopamine from a lack of natural light. There are also studies that link an increase in dopamine oxidation and the increased risk of developing Parkinson’s disease from excessive artificial light exposure. Finally, increased dopamine directly inhibits nighttime production of melatonin. What harm have we done to our health in the sake of our modern comforts?^{20 21 22 23 24}

What Are Symptoms of Improper Dopamine Homeostasis?^{25 26 27 28}

Symptoms of lower production and utilization:

• Increased appetite (cravings)
• Weight gain
• Depression
• Anhedonia
• Lack of motivation
• Lack of attention
• Cognition problems
• Compromised memory
• Elevated prolactin levels
• Lower or absent libido
• Poor bone density and health
• Parkinson’s disease
• More likely to develop gastrointestinal ulceration
• Diarrhea

Symptoms of elevated production and utilization:

• Overactive sympathetic nervous system
• Agitation
• Aggression
• Anxiety
• Paranoia
• Delusions
• Schizophrenia
• Increased or fast cognition (racing thoughts)
• Increased energy
• Insomnia
• Heightened libido
• Reward pathway seeking (addiction)
• Increased impulsive behavior
• Nausea and vomiting
• Burning mouth syndrome
• Constipation
• Increased mitochondrial oxidative stress

What Can Be Done to Reclaim Proper Dopamine Homeostasis?

Through many comforts of our modern life, we are left with wild fluctuations of dopamine and higher occurrences of dopamine oxidation significantly negatively affecting our mental and mitochondrial health. Checking social media and our E-mail excessively to see if anyone has written or praised us triggers constant dopamine releases which get us addicted. How many people are addicted to the Internet? How many people are addicted to pornography? How many people are addicted to opioids? How many people look at their phone screen, a few inches from the face, in darkness, at bedtime, for a few hours nightly? Chocolate addiction? Gambling? What can we do to help break the cycle of fluctuations and repair homeostasis?

• Break the cycle of addiction. I know it is difficult, I have witnessed addiction destroy the lives of friends and family members, as I know many of you reading have. Whether it is addiction to technology, pornography, sex, drug use (opioids, MDMA, cocaine, alcoholism, amphetamines, and nicotine), gambling, overeating, etc. all of those negatively affect your health in differing degrees of severity. If a reward pathway seeking behavior is affecting your health, your family, or community, please seek help.
• Increase exposure to natural light when possible. When you first wake in the morning open up your window blinds or curtains to allow natural light into your room to improve your circadian rhythm and homeostasis. Open window blinds and curtains in your house during the day to let natural sunlight in. Eat your lunch outside when the weather is nice. Take a walk during daylight hours.²⁹
• Limit artificial light exposure at night if possible.³⁰
• Test to see if you have a catechol-O-methyl transferase (COMT) polymorphism. The COMT enzyme catabolizes catecholamines, including dopamine. If you have no polymorphism (-,-), then you tend to have lower amounts of dopamine because you produce proper amounts of COMT. You might want to supplement the amino acid L-tyrosine to increase dopamine. I would recommend you ask your medical professional about starting with a low dosage like 500 mg in the morning on an empty stomach to see if it enhances dopamine production if you show symptoms of low dopamine and titrate your dosage as needed. Other supplements that inhibit COMT production and increase dopamine include, EGCG, hydroxytyrosol, and quercetin. If you have a full polymorphism (+,+), you tend to have higher amounts of circulating catecholamines, including dopamine. If you have this mutation you would want to avoid supplements that inhibit the COMT enzyme including EGCG, quercetin, hydroxytyrosol, tea, and dark chocolate epicatechins, luteolin, fisetin, rutin, and ferulic acid. You would also want to avoid or take smaller doses of supplements and medications that increase dopamine including L-tyrosine, Deprenyl, mucuna pruriens, SAM-E, amphetamines, opioids, nicotine, L-dopa, and modafinil. Finally, magnesium supplementation can increase COMT production as a cofactor.
• The following are some healthy lifestyle changes to help increase production when needed and they include regular exercise, a healthy sex life with your spouse, self reflection, prayer, massage therapy, accomplishing tasks and goals, and listening to music you enjoy.³¹
• Ingest a diet that supports healthy levels of the neurotransmitter. I recommend the Perfect Health Diet, the Perfect Health Diet allows protein, seafood, vegetables, extra virgin olive oil, dark chocolate, bananas, green tea, turmeric, oregano, nuts, and avocados, all which increase dopamine. The diet also is very low in refined sugar and alcohol.
• Mercury exposure can interfere with the neurotransmitter by blocking the enzyme dopamine β-hydroxylase. If you test positive for mercury burden I recommend following the Cutler protocol to detox.³²

There are several endogenous chemicals which affect digestion including:

• Serotonin
• CCK
• GIP
• Gastrin
• Secretin
• Motilin
• Dopamine
• Acetylcholine
• Gaba
• Ghrelin
• Leptin
• Histamine
• Melatonin