Scientists have uncovered a previously understudied dopamine pathway that may explain how we learn to enjoy flavors we initially dislike.
A food can become more appealing even when its flavor stays exactly the same. Researchers at UC San Francisco have identified a previously understudied dopamine pathway that helps the brain learn which flavors are worth seeking out based on what happens after nutrients reach the gut.
The study, published November 4 in Nature, reveals how a slow chemical signal connects digestion with learned food preferences. The mechanism could help explain why people develop a taste for initially unpleasant flavors, including the bitterness of coffee.
How the Gut Teaches the Brain What to Like
Dopamine helps the brain learn which experiences are rewarding, but most research has examined rapid signals that appear within seconds of external cues, such as seeing a favorite meal. The newly studied “slow” dopamine system responds to events inside the body. When digestive sensors detect nutrients such as sugar and fat, they initiate signals that can sustain dopamine release in the brain for several minutes.
“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.
Coffee provides a familiar example of how this learning may work. Although its bitterness can be unpleasant initially, repeated experiences can teach the brain to associate the flavor with caffeine’s stimulating effects. Once that association develops, Knight explained, “that coffee starts to taste a lot better.”
A Hidden Dopamine Signal in the Amygdala
To isolate the brain’s response to nutrients from its response to taste, Knight and James Grove, PhD, who was then a graduate student, delivered sugar water or a milkshake-like liquid directly into the stomachs of mice. They simultaneously measured dopamine release throughout the brain.
Nutrients entering the stomach produced a strong, sustained dopamine response in the anterior basolateral amygdala, or BLA. Although researchers already knew this region received dopamine signals, their role in learning about food was unclear.
“We could see that this dopamine is part of a different system and begin to understand its role,” Knight said.
Experiments Reveal How Food Preferences Form
The researchers next tested whether the pathway was necessary for learning. When they blocked it, the mice continued eating normally but could no longer learn that a particular unfamiliar flavor was associated with calories. This showed that the pathway was important for forming food preferences rather than simply controlling food consumption.
In a separate experiment, the researchers artificially stimulated dopamine fibers in the BLA after mice sampled a calorie-free flavor. The animals subsequently developed a preference for that flavor, even though it provided no nutritional reward.
Together, the experiments demonstrated that dopamine signaling in this region can teach mice to associate a flavor with the beneficial effects of nutrients. Artificial stimulation could substitute for the signal normally generated when nutrients reach the gut.
An Unexpected Difference Between the Brain’s Two Sides
Human brain imaging provided additional evidence of a similar response. Yale psychologist Dana Small, PhD, reanalyzed an earlier PET study involving 13 men who consumed either a milkshake or a noncaloric drink. Nutrient consumption was associated with dopamine release concentrated in the left BLA.
In another experiment, Marc Tittgemeyer, PhD, and colleagues used fMRI scans to study 38 adults after glucose consumption. They detected increased activity in the same brain region, although fMRI measures brain activity rather than dopamine release directly.
Both the mouse experiments and human imaging studies showed substantially stronger responses on the left side of the BLA than on the right. This asymmetry was unexpected because brain circuits involved in basic functions such as feeding are generally considered to operate relatively symmetrically. Knight’s laboratory is now investigating why the nutrient-related response favors the left hemisphere.
Could Scientists Eventually Change Food Cravings?
Identifying this pathway may provide new opportunities to investigate how food preferences develop and whether they can be modified. One possibility involves GLP-1 medications, which mimic a hormone produced in the gut and can substantially alter eating behavior.
The researchers did not test these drugs, so their effects on the newly identified dopamine pathway remain unknown. Knight has proposed that GLP-1 medications might reduce dopamine signaling triggered by nutrients, potentially making certain foods less rewarding over time.
Such a mechanism, if confirmed, would suggest that future treatments could influence not only hunger and fullness but also the learned associations that make particular foods desirable.
“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.
Reference: “The neural basis of flavour–nutrient learning” by James C. R. Grove, Anna M. Hakimi, Queenie Li, Jingkun Zhang, Heiko Backes, Bojana Kuzmanovic, Jaewon Choi, Violeta Ubadiah, Longhui Qiu, Zhengya Liu, Dana M. Small, Marc Tittgemeyer and Zachary A. Knight, 4 November 2026, Nature.
DOI: 10.1038/s41586-026-11229-5
This work was supported by the National Institutes of Health (grants R01-DK106399, R01-DK138127, R01-NS116626, and R01-DK145100 and F31-NS120468).
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