Study Shows Brain’s ‘Pleasure Chemical’ Triggered by Pain Too

Serotonin is released in the brain during emotionally intense of events, whether negative or positive

When most people think of serotonin, a key neurotransmitter in the brain, they think of it as a “feel good” chemical that contributes to mental well-being and happiness. Serotonin's effect on mood is why it's often a target of medications that are used to treat depression, anxiety, and other mood disorders.

Bradley Miller, MD, PhD

“Drugs that increase serotonin levels are one of the most widely prescribed types of medications in the U.S.,” says Bradley Miller, MD, PhD, an assistant professor in the Department of Psychiatry at Columbia University. “Yet, scientists still know very little about what activates serotoninergic neurons and drives them to release serotonin.”

Now a research team, led by Dr. Miller, may have discovered a clue to what drives neurons to release serotonin by studying brain patterns in mice.

Intensity of events are key

“Surprisingly, we found when we watched serotonin activity in the brain, we saw that serotonin neurons responded not only to rewarding events but also to stressful stimuli,” Dr. Miller said. “This is a departure from the view that serotonin encodes pleasure. Instead, serotonergic neurons appear to react to the salience, or intensity, of events, whether they are positive or negative.”

 The researchers’ findings appear online in the June 13 issue of the Neuron

To conduct their study, the scientists used a miniature microscope to monitor the activity of serotonergic neurons as mice underwent a variety of tasks, ranging from rewarding to stressful. The more intense the situation, the more serotonin was released.

For example, if a mouse was drinking sucrose, a highly rewarding experience, serotonin neurons would fire rapidly. The serotonin activity decreased when mice drank something more neutral like water.

What surprised the researchers was that when the mice drank quinine, a bitter and aversive stimulus, the serotonin activity increased again. The researchers found similar responses as mice navigated stressful environments and interacted socially with other mice.

 “Imaging serotonergic neurons in real time across many behaviors, really putting our finger on the pulse of the system, allowed us to make this discovery that many serotoninergic neurons respond to intense experiences regardless of if they are pleasurable or stressful,” Dr. Miller said.

Studying Serotonin Presents Challenges

The importance of serotonin—the neurotransmitter plays a key role in regulating mood, appetite, sleep, digestion, and more—has led scientists to seek ways of understanding its function, but studying it has been a challenge. Most of the cells that produce serotonin are in in the dorsal raphe nucleus, a small cell group located deep in the brain, which makes targeting it difficult.

Serotonin cannot cross the blood-brain barrier, so the brain must produce any serotonin it needs to use. Treatments for depression and other mental health issues do not supply serotonin directly but trigger reactions that can boost serotonin levels in the brain.

The Columbia researchers believe their study may have implications for the treatment of mood disorders, and other mental health conditions.

“We hypothesize that serotonin release enhances learning in response to emotionally salient events. Now that we know when serotonin is released, we can determine what the function of this activity is throughout the brain,” said Grace Paquelet, a PhD student in the Columbia Neurobiology and Behavior program and a co-author of the study. “Over the long term we hope to use this information to develop better treatments for anxiety and depression.”


Researchers from the Department of Neuroscience, Department of Statistics at Columbia, the Zuckerman Mind Brain Institute, and the New York State Psychiatric Institute, Division of Systems Neuroscience, also contributed to this study.

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