A first taste of black coffee can be surprisingly unpleasant. Its sharp bitterness is the kind of flavor our brains are naturally inclined to avoid. Yet millions of people eventually come to enjoy that same taste, often looking forward to their morning cup. What changes?
Scientists at UC San Francisco may have uncovered an important part of the answer. Their research reveals a little-understood dopamine pathway linking the digestive system and the brain, helping explain how we develop a liking for certain flavors through repeated experience.
Dopamine is a chemical messenger involved in motivation, reward, and learning. Researchers have long known that it helps the brain recognize experiences worth repeating. However, most studies have examined rapid dopamine signals that appear within seconds of encountering something rewarding, such as the sight of a favorite meal.
The new research, published November 4 in Nature, examines a different system. This slower pathway responds to information coming from inside the body, allowing the brain to learn about the benefits of food after it has been consumed.
“We’ve shown that this slow dopamine system is what drives us to learn to like certain foods over time, and we can see where and how that happens,” said Zachary Knight, PhD, professor of Physiology and senior author of the study.
The findings offer a possible explanation for why an initially unpleasant flavor can gradually become enjoyable. Once the brain connects the taste of coffee with caffeine’s stimulating effects, Knight explained, “that coffee starts to taste a lot better.”
How the Gut Sends Reward Signals to the Brain
Scientists have spent decades investigating dopamine and its influence on behavior. Its familiar, rapidly acting signals help us respond to opportunities for reward. But dopamine also operates on a slower timescale, through a system that has received far less attention.
According to Knight, this slower process largely unfolds outside our conscious awareness.
When food enters the digestive tract, specialized sensors detect nutrients, including sugar and fat. Information about those nutrients travels toward the brain, where it can produce a dopamine response that develops gradually and continues for several minutes.
To investigate this process, Knight worked with James Grove, PhD, who was a graduate student at the time. They introduced nutrients directly into the stomachs of mice while monitoring dopamine activity throughout their brains.
The researchers used either sugar water or a liquid resembling a milkshake. Delivering these substances directly into the stomach allowed them to separate the effects of nutrients from the experience of tasting food.
The results revealed a powerful, prolonged dopamine response in a specific brain region called the anterior basolateral amygdala, or BLA.
The amygdala is involved in emotional processing and learning, including forming associations between experiences and their consequences. Scientists already knew that dopamine was released in this particular region, but its purpose had remained unclear.
“We could see that this dopamine is part of a different system and begin to understand its role,” he said.
Scientists Find a Brain Circuit That Changes Food Preferences
Finding the dopamine signal was only the beginning. The researchers next wanted to determine whether it actually influenced how animals learned to prefer different flavors.
They first interrupted the newly identified pathway in mice. The animals continued eating normally, indicating that the disruption did not prevent them from consuming food. However, they lost the ability to learn that an unfamiliar flavor was associated with receiving calories.
The team then conducted the opposite experiment.
After mice tasted a flavor containing no calories, the researchers artificially activated dopamine fibers in the BLA. Remarkably, the animals developed a preference for that flavor even though it provided no nutritional reward.
In effect, stimulating the pathway reproduced the learning signal that nutrients would ordinarily generate.
Together, the experiments showed that this dopamine system plays a critical role in teaching the brain which flavors predict rewarding nutritional effects.
A Surprising Discovery in the Left Side of the Brain
The researchers also looked for evidence that a comparable process occurs in humans. Brain imaging studies conducted by Knight’s collaborators revealed a strikingly similar pattern.
Dana Small, PhD, a psychologist at Yale University, revisited data from an earlier positron emission tomography (PET) study involving 13 men. Participants had consumed either a milkshake or a drink without calories.
Her analysis found that dopamine release following nutrient delivery was especially concentrated in the left side of the BLA.
A separate study led by Marc Tittgemeyer, PhD, and his colleagues provided additional evidence. Using functional magnetic resonance imaging (fMRI), which measures changes in brain activity associated with blood flow, the researchers examined 38 adults after they consumed glucose, a simple sugar.
They observed increased activity in the same brain region.
One of the most unexpected findings was that the response was not evenly distributed between the brain’s two hemispheres.
In both mice and humans, nutrients produced a considerably stronger dopamine response in the left BLA than in the corresponding region on the right.
That imbalance surprised Knight because brain networks responsible for essential functions, such as feeding, are generally expected to work in a relatively symmetrical fashion.
Why the left side plays such a prominent role remains unanswered. Knight’s laboratory is now investigating what causes this unusual difference.
Could This Discovery Help Scientists Change Food Cravings?
Identifying the pathway provides researchers with a clearer picture of how the digestive system influences the brain’s learned responses to food. It also raises an intriguing possibility: Could scientists eventually use this knowledge to change which foods people find appealing?
One area of interest involves GLP-1 medications, a class of drugs that mimic a hormone naturally released by the gut. These medications can substantially alter appetite and eating behavior.
Knight’s team did not investigate GLP-1 drugs in the new study, so it remains unknown whether they influence the dopamine pathway the researchers identified.
Still, Knight suggests that one possible explanation for some of their effects could involve reducing the dopamine signals generated when nutrients reach the digestive system. If that happens, foods might gradually become less rewarding because the brain would receive weaker signals reinforcing their flavors.
For now, this remains a hypothesis rather than a demonstrated effect of the medications.
The broader implications extend beyond hunger and fullness. Many approaches to changing eating behavior focus on reducing appetite or increasing feelings of satisfaction after a meal. The newly mapped pathway suggests that the brain’s process of learning food preferences could eventually become another target.
By influencing how the brain connects flavors with their consequences, future treatments might someday help people develop different preferences rather than simply making them feel less hungry.
“By understanding the steps between nutrient detection in the gut and learning in the brain, it might be possible to fine-tune them to subtly change our preferences for different foods,” Knight said.
The discovery offers a new perspective on why our tastes can change over time. From learning to enjoy bitter coffee to developing a preference for calorie-rich foods, what we love to eat may depend partly on a quiet conversation between the gut and brain that continues long after the first bite.
The research was supported by the National Institutes of Health (grants R01-DK106399, R01-DK138127, R01-NS116626, and R01-DK145100 and F31-NS120468).
