Nav: Home

Dopamine's yin-yang personality: It's an upper and a downer

December 10, 2018

For decades, psychologists have viewed the neurotransmitter dopamine as a double-edged sword: released in the brain as a reward to train us to seek out pleasurable experiences, but also a "drug" the constant pursuit of which leads to addiction.

According to a new study from the University of California, Berkeley, that's only one face of dopamine. The flip side is that dopamine is also released in response to unpleasurable experiences, such as touching a hot tea kettle, presumably training the brain to avoid them in the future.

The yin-yang nature of dopamine could have implications for treatment of addiction and other mental disorders. In illnesses such as schizophrenia, for example, dopamine levels in different areas of the brain become abnormal, possibly because of an imbalance between the reward and avoidance circuits in the brain. Addiction, too, may result from an imbalance in reactions to pleasure and pain.

"In addiction, people only look for the next reward, and they will take a lot of risk to get the next shot of drugs of abuse," said Stephan Lammel, a UC Berkeley assistant professor of molecular and cell biology and the senior author of a paper describing the results in the journal Neuron. "We currently do not know the neurobiological underpinnings of certain high-risk behaviors of individuals with addiction, such as sharing drug paraphernalia despite the proven risk of mortality and morbidity associated with it. An understanding of how drugs change neural circuits involved in aversion may have important implications for the persistent nature of drug-seeking behavior in the face of negative consequences."

Although some neuroscientists have long speculated about dopamine's potential role in the signaling of aversive events, its dual personality remained hidden until recently because the neurons in the brain that release dopamine in response to rewards are embedded in a different subcircuit than the neurons that release dopamine in response to aversive stimuli.

Johannes de Jong, the first author of the study, was able to simultaneously record from both dopamine subcircuits by implanting fiber optic cannulas in two brain regions - separated by just a few millimeters - using a new technology called fiber photometry.

"Our work delineates for the first time the precise brain circuitry in which learning about rewarding and aversive outcomes occurs," Lammel said. "Having separate neuronal correlates for appetitive and aversive behavior in our brain may explain why we are striving for ever-greater rewards while simultaneously minimizing threats and dangers. Such balanced behavior of approach-and-avoidance learning is surely helpful for surviving competition in a constantly changing environment."

The newly discovered role for dopamine aligns with an increasing recognition that the neurotransmitter has quite different roles in different areas of the brain, exemplified by its function in voluntary movement, which is affected in Parkinson's disease. The results also explain earlier conflicting experiments, some of which showed that dopamine increases in response to aversive stimuli, while others did not.

"We have moved away from considering dopamine neurons as just a homogeneous cell population in the brain that mediates reward and pleasure to a more defined, nuanced picture of the role of dopamine, depending on where it is released in the brain," Lammel said.

Reward prediction errors

Most of what is known about dopamine has been inferred from studies in rodents and monkeys, where researchers recorded from cells in a specific region of the brain that only contains reward-responsive dopamine neurons. It is possible, Lammel said, that through sampling biases, dopamine neurons that respond to aversive stimulation had been missed.

According to the reigning "reward prediction error hypothesis," dopamine neurons are activated and produce dopamine when an action is more rewarding than we expect, but they remain at baseline activity when the reward matches our expectations and show depressed activity when we receive less reward than predicted.

Dopamine changes neural circuits and trains the brain - for better or worse - to pursue the pleasurable and avoid the unpleasurable.

"Based on the reward prediction error hypothesis, the established tendency has been to emphasize dopamine involvement in reward, pleasure, addiction and reward-related learning, with less consideration of the involvement of dopamine in aversive processes," Lammel said.

To dissect the different dopamine subcircuits, de Jong and Lammel collaborated with the laboratory of Karl Deisseroth at Stanford University, who developed the fiber photometry technology a few years ago.

Fiber photometry involves threading thin, flexible fiber optic wires into the brain and recording fluorescent signals given off by neurons and their axons that release dopamine. The fluorescent markers are inserted into the neurons via a virus that targets only these cells.

In previous experiments in monkeys, Lammel said, scientists had recorded from dopamine cells without knowing where in the brain the cells' axons reached, which could be areas millimeters from the cell body. Working with mice, de Jong recorded simultaneously from dopamine axons in the lateral and medial regions of an area called the nucleus accumbens, considered an integral part of the brain's reward circuits. He thus captured the activity of cells whose axons reach into these regions from the dopamine areas in the midbrain, specifically the ventral tegmental area.

To their surprise, axons in the medial area released dopamine in response to an aversive stimulus - a mild electrical shock to the foot - while those in the lateral area released dopamine only after positive stimuli.

"We have two different subtypes of dopamine cells: one population mediates attraction and one mediates aversion, and they are anatomically separated," Lammel said.

He hopes that these findings can be confirmed in monkeys and humans, and lead to new approaches to understanding and treating addiction and other brain maladies.
-end-
The work was supported by the National Institutes of Health (R01-DA042889), Brain Research Foundation (BRFSG-2015-7) and Wayne and Gladys Valley Foundation. Other co-authors of the paper are Seyedeh Atiyeh Afjei, Iskra Pollak Dorocic, James Peck and Christine Liu of UC Berkeley, Christina Kim and Karl Deisseroth of Stanford and Lin Tian of UC Davis.

University of California - Berkeley

Related Neurons Articles:

Shaping the social networks of neurons
Identification of a protein complex that attracts or repels nerve cells during development.
With these neurons, extinguishing fear is its own reward
The same neurons responsible for encoding reward also form new memories to suppress fearful ones, according to new research by scientists at The Picower Institute for Learning and Memory at MIT.
How do we get so many different types of neurons in our brain?
SMU (Southern Methodist University) researchers have discovered another layer of complexity in gene expression, which could help explain how we're able to have so many billions of neurons in our brain.
These neurons affect how much you do, or don't, want to eat
University of Arizona researchers have identified a network of neurons that coordinate with other brain regions to influence eating behaviors.
Mood neurons mature during adolescence
Researchers have discovered a mysterious group of neurons in the amygdala -- a key center for emotional processing in the brain -- that stay in an immature, prenatal developmental state throughout childhood.
Astrocytes protect neurons from toxic buildup
Neurons off-load toxic by-products to astrocytes, which process and recycle them.
Connecting neurons in the brain
Leuven researchers uncover new mechanisms of brain development that determine when, where and how strongly distinct brain cells interconnect.
The salt-craving neurons
Pass the potato chips, please! New research discovers neural circuits that regulate craving and satiation for salty tastes.
When neurons are out of shape, antidepressants may not work
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medication for major depressive disorder (MDD), yet scientists still do not understand why the treatment does not work in nearly thirty percent of patients with MDD.
Losing neurons can sometimes not be that bad
Current thinking about Alzheimer's disease is that neuronal cell death in the brain is to blame for the cognitive havoc caused by the disease.
More Neurons News and Neurons Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Uncharted
There's so much we've yet to explore–from outer space to the deep ocean to our own brains. This hour, Manoush goes on a journey through those uncharted places, led by TED Science Curator David Biello.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Dispatch 2: Every Day is Ignaz Semmelweis Day
It began with a tweet: "EVERY DAY IS IGNAZ SEMMELWEIS DAY." Carl Zimmer – tweet author, acclaimed science writer and friend of the show – tells the story of a mysterious, deadly illness that struck 19th century Vienna, and the ill-fated hero who uncovered its cure ... and gave us our best weapon (so far) against the current global pandemic. This episode was reported and produced with help from Bethel Habte and Latif Nasser. Support Radiolab today at Radiolab.org/donate.