Health

Understanding Dopamine: The Chemistry, Function, and Implications

Dopamine, referred to as DA, also known as catecholethylamine or hydroxytyramine, is an endogenous nitrogen-containing organic compound (endogenous means produced or caused by internal factors in the human body), with the molecular formula C8H11NO2, It contains four elements: carbon, hydrogen, oxygen, and nitrogen, and has a relatively simple structure. However, its function is not simple.

Dopamine is probably one of the most important neurotransmitters. Neurotransmitters are chemicals that transmit information between neurons or between neurons and effectors. Effectors refer to motor nerve endings and the muscles or glands they innervate.

Compared with hormones (another chemical substance that transmits information), neurotransmitters only act on nerve bundles, have high accuracy, fast signal transmission, and can be freely retracted and released.

In 1954, two young scientists at McGill University in Canada, James Olds and Peter Milner, were studying the effects of electrical brain stimulation on learning in the laboratory.

They buried electrodes in the reticular formation of mice and wanted to see if stimulating that area, which triggers feelings of fear, would hinder the mice’s learning. It was found that one white mouse behaved strangely. It kept returning to the corner where it was shocked, and seemed to like being shocked.

To confirm whether their suspicions were correct, they responded with an electric shock every time the rats moved to the right, away from the corner. The mouse quickly figured it out, and within just a few minutes, it had climbed to the far right corner. Apparently, mice do enjoy being shocked.

This surprised the two of them. Isn’t this part of the brain supposed to trigger the feeling of fear? Why do mice like fear? Later, they discovered that the electrode of the white mouse was buried in the wrong position and stimulated the septum.

They were so excited that they conducted further research, first training hungry mice to learn to press a lever to get food or water, and then transferring the response to pressing the lever to get an electric current. This method is called intracranial self-stimulation (ICSS), which involves implanting a thin wire connected to a lever into the brain of a mouse. The mouse can receive an electrical stimulation by pressing the lever.

Olds and Milner varied the position of the electrodes and compared how often and for how long the mice pressed the lever. There is one part that the mice press most frequently, 5,000 times per hour, and can be pressed continuously for 15 to 20 hours until they are exhausted and fall asleep. Some even stopped eating or drinking until they died.

The two believe that this part can definitely bring incomparable pleasure to the mice. Otherwise, why would they press the lever so persistently, even at the cost of their lives? So they labeled this area the “pleasure center.”

For other areas, the mice would press levers to cut off electrical stimulation. These areas are labeled as punishment or pain centers. They published their research results in a paper titled “Positive Reinforcement Produced by Electrical Stimulation of the Septal Area and Other Parts in Rats.”

Later, scientists discovered that this so-called “pleasure center” is where dopamine neurons are most densely populated.

In 1957, British scientist Kathleen Montagu first identified dopamine in the human brain.

In 1958, Arvid Carlsson and Nils Ake Hillarp were the first to realize that dopamine acts as a neurotransmitter in the regulatory center in the Chemical Pharmacology Laboratory of the Swedish National Heart Institute. The nervous system has a variety of physiological functions.

Carlson also discovered that levodopa (the precursor of dopamine) is an effective way to treat Parkinson’s disease. He won the Nobel Prize in Physiology/Medicine in 2000 and died in 2018 at the age of 95.

Since the 1950s, people have done countless studies on dopamine, and their understanding of it has become more and more profound. Because the “pleasure center” is the site with the densest concentration of dopamine neurons, people initially speculated that dopamine was the chemical substance that brings happiness to people, and called it a “molecule of pleasure”. The neural circuit that produces dopamine is called the “reward system.”

Experiments on drug addicts further solidified dopamine’s reputation. Researchers injected drug addicts with cocaine mixed with radioactive sugar to see which parts of the brain burned the most calories. They found that the higher the activity in the dopamine reward circuit, the more intense the pleasure the subjects experienced. When cocaine is eliminated, dopamine activity decreases and the pleasure subsides. Apparently, drugs make people happy through dopamine circuits.

However, this immediately raised a question. It took millions of years for humans to evolve to what they are now. Does this precious dopamine circuit only exist for drug use? Or to express it in the language of God’s creation of man, did God create this dopamine circuit just for people to take drugs? This obviously doesn’t make sense. Drugs must have cunningly hijacked a circuit for which it was not designed.

So according to the design, what should trigger this loop? Could it be food? Researchers put food in cages for mice at regular intervals, and the mice enjoyed it happily. The electrodes showed that their dopamine circuits were indeed activated. However, within a few days, when the mice were happily eating, the dopamine circuits were no longer active.

This refutes the previous assumption that dopamine is a “happy molecule”. If so, then when the mice eat happily, the dopamine circuit should be in an excited state, but it is not. This suggests there is no causal relationship between dopamine and happiness.

Why was the dopamine circuit activated in this experiment at first, and then turned off again after continued feeding?

Experiments by Wolfram Schultz, professor of neuroscience at the University of Cambridge, provide the answer. Schultz was one of the most influential pioneers in experimental research on dopamine. He became interested in the role of dopamine in learning while he was a professor of neurophysiology at the University of Friborg in Switzerland.

He put the macaques into a device with two light bulbs and two boxes. Every once in a while, a light bulb will light up. One of the lights means there is food in the box on the right, and the other light means there is food in the box on the left.

It took the monkey some time to find this pattern. They would open the box randomly at first, and of course they would find the right one only half of the time. After a while, the monkey figured out the pattern of signals and could directly and accurately find the box with food.

At this time, Schultz discovered a strange phenomenon. The monkeys’ dopamine circuit was activated not at the moment they ate food, but at the moment the light turned on.

Clearly, it’s not food that activates dopamine circuits, so what is it?

Schultz proposed a new hypothesis: dopamine is activated by “surprise”. The so-called “surprise” is the positive prediction error, that is, the actual reward minus the expected reward is positive. In other words, dopamine is not a pleasure maker, but a response to uncertainty, possibility, and anticipation.

If this hypothesis is true, then in Schulz’s experiment, it is assumed that there is no uncertainty about the two lights lighting up alternately from time to time, but there is only one light. When the light is on, there must be food in the box. Then after a period of time, when the light is on, , the monkey’s dopamine circuits were also not activated, just like the mice in the previous experiment.

This period of time can be called the “dopamine fatigue period”. It is hard to say how long this period will be. For mice, it is a few days, for monkeys, it may be more than ten days or dozens of days, and for humans, it may be longer.

The impact of uncertainty on animal behavior actually dates back to the 1960s, when American psychologist and founder of new behaviorist learning theory Burrhus Frederic Skinner ), conducted a famous pigeon experiment.

He put the pigeons in the box and installed a lever device so that the pigeons could get food with every peck or a few pecks. Sometimes the experiment is set to require one peck, sometimes it is set to require ten pecks. In the experiment that required one peck, the pigeons pecked the lever leisurely; in the experiment that required ten pecks, the pigeons also pecked the lever leisurely.

Then Skinner changed the game by making the number of lever presses required to release the food random, rather than a fixed one or ten. At this time, an interesting phenomenon occurred. The pigeons became excited and pecked quickly.

What factors prompted them to make greater efforts? It’s obviously uncertainty.

The design standard for modern casinos is to devote up to 80% of their floor space to slot machines, which contribute the majority of the casino’s revenue. The biggest feature of slot machines is uncertainty. If they spit out coins on a regular basis, there wouldn’t be so many people sitting there playing all day long without eating or drinking.

It’s true that uncertainty is the essence of gambling, but other gambling projects don’t display the pure uncertainty that slot machines do, that is, the outcome has no connection to your actions. When playing other sports, the result is more or less related to your decision-making. For example, when playing blackjack, you decide to add cards, and the result is bust; if you decide not to add cards, you may win. However, slot machines do not require you to make any decisions, and the results have nothing to do with your decisions. This is the most addictive and dopamine-filled.

Why does dopamine have this property? Let’s first take a look at the responsible role of dopamine. Once we understand its essence, it will be easy to understand its characteristics.

Dopamine’s job is to get you moving, to explore and even take risks in order to obtain the resources necessary for survival: food, sex, social recognition….

From an evolutionary point of view, this is necessary. If there was a kind of people who didn’t want to look for food when they were hungry and were not attracted to the opposite sex of the right age, this kind of people would have become extinct long ago.

So once you take action, can you get food, sex, and social recognition? This dopamine is not guaranteed. It is only responsible for making you take action. It doesn’t care what the result is, whether you will be happy or not. Maybe you will be happy, maybe not. Anyway, sometimes it acts rogue and there’s nothing you can do about it.

It doesn’t care whether the happiness you get is good for you. If you keep eating and become a big fat man unable to move, that’s not its business. It’s only responsible for you not to starve to death without looking for food.

In 1989, Kent Berridge, a professor of psychology and neurology at the University of Michigan, conducted an experiment in which mice were injected with a toxin that could kill dopamine-receiving cells. After blocking dopamine, all mice The white rats no longer did anything, could not move around, and did not even eat. However, when the experimenter dropped some sugar water into the mouths of the white rats, they could still enjoy the food and lick their lips to express happiness. When experimenters injected dopamine into the brains of mice, they drank more sugar water but did not lick their lips more to express happiness.

This experiment has actually proven both positive and negative that dopamine prompts animals to take action in anticipation of a reward, but cannot feel the joy of receiving a reward.

In 2001, Stanford neuroscientist Brian Knutson conducted an experiment in which subjects were shown a screen and told that when a certain symbol appeared on the screen, they could win money by simply pressing a button. He scanned the subjects’ brains and found that as soon as the symbol appeared, the “reward center” that released dopamine responded, and the subjects pressed the button and got their reward. But when the subjects actually won money, the “reward center” became quiet and another area became active. This is the real “happy center.”

Later, scientists discovered that what activates this real “pleasure center” are neurotransmitters such as oxytocin, serotonin, endorphins (equivalent to the brain’s own morphine), and endocannabinoids (equivalent to the brain’s own cannabis). They combine to create the feeling called “happiness” you have after obtaining survival resources such as food, sex, and social recognition.

Knudson’s experiment is actually the human version of Schulz’s monkey experiment. When the monkey saw the light on, he knew which box the food was in. Even though he hadn’t opened the box and eaten the food, the “reward center” was already excited. When I actually ate the food, the “reward center” was quiet.

It can be seen that what dopamine sells is the hope, promise and desire of happiness, not happiness itself. Of course, genes will always give you a little sweetness in order to keep you playing the game of copying them. Otherwise, it would be too selfish and dangerous, and you might go on strike. For example, patients with depression cannot feel happiness and are in pain. Will commit suicide.

In short, the dopamine circuit is neither a “pleasure circuit” nor a “reward circuit,” but a “motivation circuit” that motivates you to act by promising pleasure but not guaranteeing that you will receive it. Its purpose is to maximize the use of resources to ensure survival and reproduction, not to ensure that you are happy.

This role of dopamine also determines that it is very sensitive to uncertainty, “loving the new and hating the old”, and it is too lazy to deal with things it has already understood and acquired. That’s why once the mice master the feeding schedule, their dopamine circuits shut down. Because the monkeys don’t know which light will come on next, their dopamine circuits remain excited. This is especially true for people, who sit in front of the unpredictable slot machines for days at a time.

This is why Zhang Ailing said: “Perhaps every man has had two women like this, at least two. If you marry a red rose, over time, the red will be like a smear of mosquito blood on the wall, and the white will be the moonlight in front of the bed. ‘;Married to a white rose, the white one is like a grain of rice sticky on the clothes, but the red one is a cinnabar mole on the heart.”

Dopamine not only likes the new but dislikes the old, it does so very quickly. Don’t bother to think more or take another look at something you already control. The “dopamine fatigue period” is very short.

This is why when people in Knudson’s experiment saw symbols that could win money appearing on the screen, and when monkeys in Schultz’s experiment saw the lights turn on, the dopamine circuit was immediately excited, asking you to press the button and letting the monkey open it. This box. But the moment you start taking action, the dopamine circuit immediately quiets down. By the time you actually win money and eat food, this part is no longer active.

Dopamine’s strategy is completely correct. Energy cannot be wasted in the known world or in the present. Energy must be saved and focused to conquer the unknown world and the future. Only in this way can the probability of survival and reproduction be improved. . It’s other neurotransmitters that make people feel happy.

If a person pays too much attention to the present and enjoys the feeling of happiness without exploring the future, then his happiness cannot last long. As the saying goes, “If a person has no long-term worries, he must have immediate worries.” Over millions of years, those who only focus on the present and do not plan for the future will surely become extinct long ago.

This is why people today always feel that desire is so strong and long-lasting, while happiness is so slight and short-lived. Dopamine makes you restless and makes you unable to sleep or eat well. It’s almost impossible to live happily in the present.

Of course, dopamine also makes sense. The prerequisite for living in the present is to live in the present.

Humans are slaves to genes. The purpose of genes is to use you to reproduce and reproduce themselves, not to make you live a long, healthy and happy life. From a genetic point of view, it is best for a person to live non-stop until the age of 36 and then die immediately to make room for the next generation of genetic replication tools.

Given this property of dopamine, if a marriage is to remain stable, the wife must not be too virtuous, because the husband will “take it easy if it is easy to get.” This really cannot be blamed on the husband, even mice and monkeys do this. Therefore, the wife can only find a way to solve this problem by herself. She can “do it” from time to time to increase uncertainty and unavailability and stimulate her husband’s dopamine circuit.

Of course, this refers to people with normal dopamine circuits. If the dopamine circuits are abnormal, that is a different story.

Mick Jagger is a British rock singer and a founding member of the Rolling Stones. He has been the lead singer of the band since 1969. He was knighted at Buckingham Palace in 2003. He told his biographer in 2013 that he had had sex with more than 4,000 women, which meant that he had changed partners every five days on average in his adult life, and his “dopamine fatigue period” lasted only five days.

In the American TV series “Seinfeld”, George falls in love in almost every episode and imagines every new woman he meets as a potential lifelong partner. But as long as the woman repays him with true love, he will no longer be crazy about her and abandon her. Keep looking for the next one. When his fiancée dies after licking the poisonous glue on her wedding invitation, instead of being shocked and grieving, he is ecstatically ready for a new relationship.

Clearly, both are cases of lesions in dopamine circuits. There is also a famous case involving Parkinson’s disease that provides a deeper understanding of the dangers of pathological dopamine circuits.

We know that the central dopaminergic system (especially the nigrostriatal tract) plays an important role in body movement, and its transmitter release may be the basic condition for all behavioral responses. Excitation of this system can cause reactions such as curiosity, exploration, foraging, and increased movement; inhibition of this system can cause reactions such as decreased movement; damage to this system will cause the loss of all behavioral reactions and a state of stupor, lying there motionless like a dead person. Except for the eyeballs.

The main pathological changes in Parkinson’s disease occur in the ventral part of the substantia nigra of the midbrain. This area contains a large number of dopamine neurons and signals to the basal ganglia of the brain. Patients with Parkinson’s disease experience a massive death of neurons in the pars compacta, leading to a lack of dopamine and malfunction of neural circuits such as movement and limbic systems.

As mentioned earlier, in the 1960s, Arvid Carlson had discovered that levodopa was an effective way to treat Parkinson’s disease. To this day, levodopa remains the mainstay drug in the treatment of Parkinson’s disease.

On March 10, 2012, a Parkinson’s disease patient in Melbourne, Australia, sued Pfizer, claiming that its drug cabergoline (Cabaser) made him lose everything. Cabergoline treats Parkinson’s disease through dopamine receptor agonism. He started taking the drug in 2003, and after increasing the dosage in 2004, he became addicted to video poker machines. He spent all his retirement money on gambling, sold his car, pawned most of his belongings, borrowed money from relatives and friends, took out bank loans, and sold his house. He lost a total of 100,000 US dollars, and he still couldn’t stop. Come down.

In 2010, he read an article about a link between Parkinson’s disease drugs and gambling and decided to stop taking cabergoline, and soon the gambling stopped.

Another risk with Parkinson’s disease medications is hypersexuality. The Mayo Clinic documented the embarrassing experience of a 57-year-old man receiving levodopa.

These cases tell us that lesions in the dopamine circuit can lead to serious addictive consequences such as pornography, gambling, and drug addiction, and some may even lead to death. As mentioned earlier, Olds and Milner’s experiments on white mice showed that they would not eat or drink, but kept pulling the lever to stimulate the dopamine circuit until they starved to death.

You might think it’s a mouse, but people can’t be that stupid. Robert Heath of Tulane University in the United States implanted electrodes in the brains of subjects and gave them a control box that allowed them to stimulate their own “pleasure center”. They could choose the frequency of stimulation. As a result, they shocked themselves an average of 40 times per minute.

During the break, the researchers brought them food. Although the patients admitted that they were hungry, they were still unwilling to stop the electric shock to eat. When the experimenter proposed to terminate the experiment, one patient protested strongly. Another subject continued to press the button more than 200 times after the current was cut off, until the experimenter asked him to stop.

In the face of the surging dopamine, people’s IQ and willpower are like snow lions turning toward fire, melting instantly.

If the dopamine circuit is completely inactive, a person will be in a state of stupor, without any ability to move, and can only wait for death; if the dopamine circuit is not active enough, a person will develop symptoms such as depression, and be passive and pessimistic and seek death; if the dopamine circuit is too active, a person will suffer from mania, In diseases such as schizophrenia, there is no distinction between life and death; dopamine circuits are extremely active, and people will activate various self-destructive modes such as addiction and act until death.

Success is dopamine, failure is dopamine. It is a blessing and a curse.

Everyone is born with a different “factory configuration” of dopamine. Some people have a higher configuration, which is easier to balance, and some people have a lower configuration, which is harder to balance. However, almost everyone struggles on the dopamine spectrum in order to find a balance and live a peaceful life.

Understanding these knowledge and principles may help you find a balance.

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