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a gray mouse drinking from a water bottle in a cage
gray mouse drinking from water bottle in cage

“Feel-Good” Neurons Steer Mice Toward Hydration-Boosting Liquids

The cells signal to the brain how hydrating particular beverages are, but it’s not yet clear whether they play a similar role in humans.

Shafaq Zia
Shafaq Zia

Shafaq Zia is a freelance science journalist and a graduate student in the Science Writing Program at the Massachusetts Institute of Technology. Previously, she was a reporting intern at STAT, where she covered the COVID-19 pandemic and the latest research in health technology.

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Dopamine, a “feel good” chemical, is released in the brain when we eat high-fat and sugary delights that taste good. However, it may also guide our food and drink choices through a mechanism that has nothing to do with taste,  a recent mouse study finds.  

A team of researchers at the University of California, San Francisco (UCSF), describe the new mechanism in a paper published July 13 in Nature. They report that dopamine-releasing neurons in a region of the brain called the ventral tegmental area (VTA) that is important for reward-seeking behavior, motivation, and aversion are activated by hydration.  

This mechanism, the researchers say, explains how animals learn to prefer one type of food over another in order to survive in the wild. “Many animals actually get most of their water from food,” says study coauthor James Grove, a neuroscientist at UCSF. “So they presumably have to learn through experience which foods are rehydrating and what they should eat when they’re thirsty.” To understand which neural mechanisms in the brain might associate the tastes of foods and liquids with their effects after absorption into the bloodstream, the researchers turned to mouse experiments.   

Using technology that allowed them to look at the activity of individual VTA neurons in the mice, the scientists gave thirsty animals unrestricted access to water for five minutes and observed how their neural activity changed. The mice voraciously drank water, and dopamine neurons in the VTA became active as a result of this rewarding stimulus—a mechanism that was already well-established in previous research.  

However, to the researchers’ surprise, there was a second wave of neural activity that emerged 10 minutes after the mice first started drinking. The animals no longer had access to the water, so this activity was unrelated to taking in the liquid. Instead, the researchers hypothesized, it was the dopamine neurons informing the brain about how hydrating the liquid is based on the effects it had on the concentration of dissolved minerals in the mice’s blood.  

[Animals] presumably have to learn through experience which foods are rehydrating and what they should eat when they’re thirsty.

—James Grove, University of California, San Francisco

When the researchers repeated the experiment, they gave the mice salt water, which is dehydrating. This time, a much smaller percentage of dopamine neurons were activated after the liquid began to absorb into the mice’s bloodstream, they found. And when they bypassed the act of drinking completely by infusing unsalted water through a catheter attached to the mice’s stomachs, the hypothesis was confirmed—the second wave of dopamine neural activity was in response to the internal effect of water, not its taste.  

To test whether the neural feedback had a lasting impression on the mice’s drink preferences, Grove and his team developed a system in which they gave the mice two bottles of differently flavored liquids; each lick of one type of flavored liquid triggered the infusion of dehydrating salt water into a mouse’s stomach. With each lick of the other flavored liquid, unsalted, hydrating water was infused. After three one-hour training sessions, the catheters were removed and the mice’s preferences were tested again using the two bottles. The animals gravitated toward the flavored liquid that had been paired with the infusion of unsalted water.  

Taken together, these results, the researchers say, suggest that a group of dopamine-releasing neurons in the mice’s VTA track how effective beverages and foods are at meeting their body’s needs and steer their future choices accordingly.  

Even though the study used mice and not people, Grove says it “establishes the logic for why and how food and drink preferences are acquired.” With more research, this understanding, he says, may help in devising ways to combat the addictive effects of snacks like chips and soda.  

Abigail Polter, a microbiologist at the George Washington University who studies the effects of stress in the VTA and was not involved in the new study, says the findings move forward researchers’ understanding of dopamine in exciting ways. “It really shows that dopamine is also responsive to what is going on inside the body and not only to external stimuli,” she says.   

Polter concurs that the reliance on an animal model is a limitation of this study, as the relevant neural mechanisms are likely to be far more complex in humans. But she says the findings are “an opportunity for the researchers to start looking at how these internal states and external stimuli integrate.”  

While investigating whether and how this mechanism works in humans is important, Grove says, there’s a lot more that needs to be done before that. The next step for the research team, he says, is to delve deeper into the changes that take place on a cellular level in the animal’s brain that enable the neurons to drive future food preferences. 

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