DOPAMINE: The Brain Chemical Linked to Mood and Pleasure —May Have Other Functions Too

DOPAMINE: The Brain Chemical Linked to Mood and Pleasure —May Have Other Functions Too 

For decades, discussions about dopamine centered around how this hormone provides people with a feeling of pleasure and rewards. Now, a new study by researchers at Northwestern University found that one genetic subtype of dopamine does not respond to rewards at all, but responds when the body moves.

The investigators say this information opens new research directions for further understanding and potentially treating Parkinson’s disease, a condition which scientists believe is caused, in part, by a loss of dopamine neurons in the brain.

Besides being a hormone, dopamine is also a neurotransmitter because it carries messages from one neuron, or nerve cell, to the next neuron. Studies have found that dopamine works with other neurotransmitters in coordinating the nerve and muscle cells involved in movement.

The release of dopamine, also known as the “happy hormone,” has been associated with pleasurable experiences, such as shopping, winning a game or enjoying good food. These pleasant experiences, in turn, create a reward system in the brain. For example, when you’re eating a delicious meal at a restaurant, your brain releases dopamine. And, because this experience makes you feel good, you—and your brain—will consider it a reward when you return to the restaurant and expect to eat the same delicious meal.

The research team at Northwestern’s Dombeck Lab said they established three types of dopamine subtypes, two tracked rewards and aversive events while the third monitored movement. The investigators used mice in their study, which was published August 3 in the journal Nature Neuroscience.

Team members discovered that one genetic subtype of dopamine neurons fired when the mice started running faster. This subtype, however, did not respond to rewards.

“When people think about dopamine, they likely think about reward signals,” Northwestern’s Daniel Dombeck, who co-led the study, said in a press release. “But when the dopamine neurons die, people have trouble with movement. That’s what happens with Parkinson’s disease, and it’s been a confusing problem for the field.”

Dombeck noted that the dopamine subtype that signals movement without any reward response is in the same location of the midbrain where dopamine neurons first die in Parkinson’s disease.

“That’s just another hint and clue that seems to suggest that there’s some genetic subtype that’s more susceptible to degradation over time as people age,” Dombeck said.

The Northwestern team further noted that the dopamine neurons that survive are correlated with the animals slowing down.

“We’re wondering if it’s not just the loss of the motor-driving signal that’s leading to the disease—but the preservation of the anti-movement signal that’s active when animals decelerate,” Dombeck said in the press release. “It could be this signal imbalance that strengthens the signal to stop moving. That might explain some of the symptoms. It’s not just that patients with Parkinson’s can’t move. It could also be that they are being driven to stop moving.”

Seeing activity when the mouse accelerated but not seeing activity in response to a rewarding stimulus goes against the dogma of what most people think these neurons should be doing, said Rajeshwar Awatramani, who co-led the study with Dombeck.

“Not all dopamine neurons respond to rewards” Awatramani said in a press release. “That’s a big change for the field. And now we found a signature for that dopamine neuron that does not show reward response.”

What is Parkinson’s Disease?

Parkinson’s disease is a progressive disorder caused by denegeration of nerve cells in the part of the brain called the substantia nigra (sub-STAN-she-uh NYE-gruh), which controls movement, according to the American Parkinson Disease Association (APDA). Because Parkinson’s is a chronic and progressive disease, symptoms like tremors, stiffness or rigidity of the muscles, and slowness of movements become worse over time.

An estimated 1 million people in the United States and more than 10 million people worldwide are living with the disease, the APDA reports. Most people develop Parkinson’s disease symptoms after the age of 50.

The APDA explains that the loss of cells in the substantia nigra (which is Latin for “black substance”) distinguishes Parkinson’s disease from other movement diseases. The neurons in this area appear dark when placed under a microscope. These dark neurons produce dopamine, which helps to regulate movement. Because of the loss of dopamine, many Parkinson’s disease treatments attempt to increase dopamine levels in the brain, according to the APDA.

Different Dopamine Subtypes Have Different Functions

Kimberlee D’Ardenne, an assistant research professor in psychology at Arizona State University, who was not involved in the new study, said she has conducted research of her own measuring areas in the brain where dopamine neurons are located.

D’Ardenne said scientists once thought dopamine neurons did not respond to aversive events. However, studies published about 15 years ago found that dopamine neurons respond to negative events, like a puff of air against the eye or a mild electric shock or losing money, she said.

“These studies showed that some dopamine neurons respond only to rewards while others respond to both rewards and negative experiences, leading to the hypothesis that there might be more than one dopamine system in the brain,” D’Ardenne wrote in an article for The Conversation.

After these studies came experiments showing that there is more than one type of dopamine neuron, according to D’Ardenne. So far, researchers have identified seven distinct types of dopamine neurons by looking at their genetic profiles, D’Ardenne said. But the study by the Northwestern University researchers was the first to parse dopamine function based on neuron subtype, she added.

According to D’Ardenne, the Northwestern University researchers’ identifying the movement-related dopamine neurons that are among the hardest hit in Parkinson’s disease, while two others types are not as affected, might lead to more targeted treatment options for Parkinson’s.

Awatramani said the researchers are “still trying to figure out what this all means.”

“I would say this is a starting point. It’s a new way of thinking about the brain in Parkinson’s,” he said.

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