Written by: Kane York

Illustrated by: Emma Thornton-Kolbe

Editors: Christian Greenhill, Kristen Loesel, and Jennifer Baker

Hey there, reader! This is the first in a series of articles addressing common myths about the brain. You can find my previous article here, in which I discuss the complexity of depression. Expect more to be coming soon! Enjoy reading.

Imagine eating a jelly donut. Imagine your first kiss. Imagine getting a good performance review from your boss. In each case, you may feel a sense of happiness, joy, or pleasure. Now, think about the brain functions that cause these happy feelings. You might guess that each of these scenarios triggers an instant boost of dopamine and serotonin in your brain. Dopamine and serotonin are two of the most talked about (and two of the most misunderstood) neurotransmitters, the chemicals that brain cells use to communicate. Yes, dopamine is associated with pleasure and serotonin with mood, but to stop there would be missing the full picture. Like many myths, there is some truth here. However, these molecules have a much richer role in the body and behavior than just the happy feelings.

Neurotransmitters are the chemical language of brain cells

Before discussing the effects of these neurotransmitters in detail, it’s important to understand how brain cells, or neurons, communicate. Most of the magic starts at the synapse, the point where two neurons meet (Figure 1). When a neuron is activated (due to, let’s say, eating a jelly donut), neurotransmitters (e.g., dopamine, serotonin) are released into the synapse. The neurotransmitters quickly make contact with receptors on neighboring neurons. This interaction of neurotransmitters and receptors either increases or decreases the chances of the second neuron’s activation, depending on the neurotransmitters released and the receptors that detect them. In this way, dopamine, and serotonin act on pathways in the body that affect happiness, both directly and indirectly. 

Figure 1: An illustration of a synapse, the point at which two brain cells, called neurons, meet.
Illustration by Kane York

Dopamine: More Than Just Pleasure

So, dopamine is the neurochemical correlate to all our pleasure, right? Well, it’s complicated. When we feel rewarded, do our dopamine levels increase? Yes, but not always. Dopamine can also be thought of as a “learning molecule”. The midbrain—the topmost part of the brainstem, which connects the brain to the spinal cord—dopamine system is like a “reward predictor”, rather than just a simple on/off switch for pleasure. If you receive an unexpected reward, like a piece of chocolate when arriving at work, dopamine levels will likely increase as you eat the candy. However, if chocolate is expected (e.g., if you work at a candy factory), your dopamine response may be lower. This is true even if you are enjoying the candy! Dopamine records the results of the brain’s predictions about expecting chocolate. If your brain’s prediction is correct, recording the results is not needed, and dopamine levels stay low. If more reward was obtained than predicted, dopamine levels shoot up. 

Not only do dopamine levels increase when receiving an unexpected reward, dopamine levels also increase in the presence of something that predicts a reward. In a classic study, researchers trained monkeys to perform a behavioral task to get a reward (in this case, pushing a lever to get apple juice). Consistent with the researchers’ predictions, dopamine levels were high at initial deliveries of apple juice, but declined when the juice became expected. Then, the researchers introduced a light that would activate one second before the monkeys were primed to press the lever. Dopamine responses began to increase at the presentation of the light, not at consumption of the apple juice. In other words, the signs that predict the reward (the light), not the experience of the reward (drinking the apple juice), caused a dopamine spike. Keep this “encoding effect” in mind the next time you see an advertisement for candy–you are “receiving” dopamine before you experience the taste of the sugary treat!

Aside from dopamine’s direct effects on happiness via reward prediction, dopamine is also involved in movement. For example, Parkinson’s disease is characterized by the degradation of dopamine-producing neurons in the basal ganglia. The basal ganglia are a cluster of neurons that connect to the brain’s motor cortex to assist with initiating or inhibiting muscle-motor movements (e.g., writing, lifting a cup to drink). Dopamine acts on two pathways in the basal ganglia—the one that initiates movement (the direct pathway) and the one that inhibits movement (the indirect pathway). Remember, neurotransmitters like dopamine activate or inactivate neurons by binding to receptors that have different functions. In this case, the direct pathway has activating receptors and the indirect pathway has inactivating receptors, both of which interact with dopamine to turn neurons on or off. 

In a healthy person, high dopamine levels turn on the neurons with activating receptors and turn off the neurons with inactivating receptors, resulting in the desired amount of movement. But for those with Parkinson’s, dopamine levels are low, and thus, the direct pathway doesn’t produce enough movement and the indirect pathway inhibits movement too much. This loss of equilibrium disrupts movement processing and produces the trademark tremors associated with Parkinson’s.

Figure 2: Dopamine and serotonin carry lots of messages all over the brain and body. 
Illustration by Emma Thornton-Kolbe

Serotonin: More Than a Good Mood

Serotonin is typically credited for its role in our good days and gleeful moods. Interestingly, our main evidence for serotonin’s involvement in mood is the relief of depression and anxiety via selective serotonin reuptake inhibitors (SSRIs). My previous article touches on this in more detail but to be brief, SSRIs lead to serotonin accumulation in the brain  , resulting in serotonin stimulating neurons more often. SSRIs are thought to be helpful in people with depression since this demographic has been observed to have decreased amounts of serotonin and lower efficiency serotonin transporters, which increases the risk of developing depression. Consistent with this, SSRIs have been reported to be 20 to 30 percent more effective than placebo groups for people with depression, and have been shown to improve anxiety as well. 

Even though SSRIs help with mood disorders, this does not necessarily mean that serotonin is a direct neurochemical correlate of mood. For example, it is possible that the serotonin system in people with mood disorders is comparable to that of healthy people, but increasing the system’s activity still helps to improve mood. Additionally, when looking at the post-mortem brains of people with depression, low serotonin levels are not a consistent pattern, and lowering tryptophan (the chemical that is turned into serotonin) in one’s diet does not result in a mood disorder. Because of these complicating issues, it is not fully clear how serotonin contributes to mood, but one thing that is clear is that the functions of this molecule are much more diverse than typically perceived.

Like dopamine, serotonin serves a wider variety of functions in the body than its primary claim to fame. Serotonin is involved in the regulation of appetite and body temperature, which are both related to metabolism, the body’s way of converting food into energy. Serotonin systems in our hypothalamus, a dense region of neurons at the base of the brain, can activate one set of neurons that decrease appetite and deactivate another set of neurons that increase appetite. In one study, researchers decreased serotonin levels in the brains of rats, resulting in overeating and obesity. The hypothalamus also interacts with serotonin-producing neurons in the spinal cord that are indirectly involved in the activation of brown adipose tissue, fat tissue near the base of the neck that generates heat. Regulation of body temperature via brown adipose tissue is especially important when increases in body temperature are necessary for survival, such as hibernation in animals, decreased food intake, hypothermia, or fever. This effect of serotonin helps explain what is going on as we enjoy winter holiday meals. A decrease in serotonin fuels that desire for stuffing and the presence of this molecule is, in part, responsible for warming us up in this cold weather!

Like dopamine’s role in skeletal muscle movement and Parkinson’s, serotonin also plays important roles in muscle contraction. Serotonin receptors are present in different muscle-containing organs throughout the body, including the gut and the heart. For example, serotonin stored in the cells of the gut wall makes up around 90% of the total amount of serotonin in the human body. When these serotonin stores are released following food consumption, it triggers peristalsis, the muscle contractions that move partially digested materials through the gastrointestinal tract. Interestingly, one type of serotonin receptor involved in gut peristalsis, known as 5-HT4, is also found in ventricles of the heart. High levels of serotonin and their interaction with the 5-HT4 receptor have been linked to irregular heartbeats and heart chamber remodeling. It seems that serotonin plays both a normal role in heart function and repair, and, like many other things, a dysfunctional role if the system becomes imbalanced.

Related to the heart, serotonin is also linked to the cardiovascular system in a process known as hemostasis—the stopping of bleeding. When you cut your skin, blood begins to clot around the wound to close it. Typically, platelets—cell fragments that contribute to clotting—release serotonin which stimulates further clotting. As you would expect, platelets with low amounts of serotonin have a harder time coming together to close wounds. In fact, SSRIs can actually exacerbate bleeding because the medications decrease the ability of platelets to acquire serotonin! Serotonin also plays a role in the pain you feel when you cut your skin. When there is tissue damage, serotonin assists in facilitating the pain signal. It’s quite ironic that serotonin, the often-assumed “happy chemical,” can communicate something so unhappy to us! 

Are dopamine and serotonin really the “happy chemicals”? 

Returning to the central question: are dopamine and serotonin really the “happy chemicals”? Yes, both directly and indirectly. Directly, because both molecules are involved in pleasure and mood, and indirectly because of all the other roles dopamine and serotonin serve in the body. All of these functions—reward prediction, mobility, appetite, body temperature, clotting, and more—contribute to our overall sense of well-being. While they do influence our happiness, it is clear that dopamine and serotonin are not just “happy chemicals”.

Note: Illustrations for this article were created using BioRender.

A. Kane York is a Neuroscience Ph.D. candidate in Dr. Giancarlo Vanini’s lab, where he studies the neural circuitry of sleep. When he’s not in the lab, Kane occupies his time with video games, non-fiction books, and D&D. Kane is dedicated to science communication and hopes to show that science is one of the best endeavors humans have embarked upon.

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