How the Gut-Brain Dopamine Pathway Controls Learned Food Preferences Over Time
If you can remember your first sip of coffee, the memory might not be a pleasant one because coffee’s bitter flavor is something we naturally steer clear of. The answer to how coffee fans learn to love it may lie in an understudied slow dopamine pathway connecting the gut and brain. Research conducted at the University of California, San Francisco and published Nov. 4 in Nature demonstrates that this circuit assists the brain in linking a taste to the positive results that occur after consumption.
For a long time, researchers have suspected that dopamine contributes to this form of learning, yet the majority of dopamine studies have concentrated on rapid signals activated within seconds by external cues, such as the sight of a preferred meal. The new study investigates a much slower dopamine pathway that responds to signals coming from within the body. Zachary Knight, a professor of physiology and senior author of the study, explained that this slow system drives us to learn to like certain foods over time.
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.
— Zachary Knight, PhD, Professor of Physiology, University of California, San Francisco
Once your brain learns to associate the flavor of a favorite brew with the uplift from caffeine, Knight noted that the coffee starts to taste a lot better. Dopamine helps guide behavior by teaching what is worth pursuing, yet the slower side to dopamine remains much more of a mystery in daily life. Sensors in the digestive system detect nutrients such as sugar and fat, sending signals toward the brain that build after food reaches the gut and persist for many minutes.
Isolating Gut Responses in Mice and Human Brain Imaging
To investigate that signal, Knight and James Grove, PhD, who was then a graduate student, infused substances like a milkshake-like liquid or sugar water directly into the stomachs of mice while tracking dopamine activity across the brain. By avoiding the mouth entirely, the researchers were able to single out the brain’s reaction to nutrients arriving in the gut without any influence from taste. The nutrients triggered a strong and sustained release of dopamine in the anterior basolateral amygdala, or BLA.
When the researchers blocked this pathway, mice continued eating normally but could no longer learn that a particular new flavor predicted calories. On the other hand, when the researchers artificially activated dopamine fibers in the BLA following the consumption of a calorie-free taste by mice, the animals developed a preference for it, meaning the stimulation successfully replaced the actual nutrients. Human brain imaging by Knight’s collaborators showed a similar pattern. Dana Small, PhD, reanalyzed an earlier PET study of 13 men who consumed either a milkshake or a noncaloric drink and found that dopamine release concentrated in the left side of the BLA after the nutrients reached the gut. In a separate experiment, Marc Tittgemeyer, PhD, and colleagues used functional magnetic resonance imaging in 38 adults and found increased activity in the same region after they consumed glucose.
Asymmetry in Neural Circuits and Future GLP-1 Implications
In both mice and humans, the researchers observed that nutrients produced a much stronger dopamine response in the left BLA than in the right. This asymmetrical reaction came as a surprise, given the common assumption that neural networks responsible for fundamental processes like eating function equally on both sides of the brain. The reason this system prefers the left side is a question that Knight’s lab is currently trying to answer.
Mapping the pathway gives scientists new places to investigate how food preferences are learned and perhaps eventually modified. One intriguing question involves GLP-1 drugs, which mimic a hormone produced in the gut and can dramatically change eating behavior. Knight’s team did not study GLP-1 drugs, and whether they affect the newly identified pathway remains unknown. However, Knight speculates that the medications could potentially reduce nutrient-triggered dopamine signaling, making food less reinforcing over time.
That raises a broader possibility that future treatments might someday influence the underlying learning process that makes some foods particularly desirable, rather than simply affecting how hungry or full someone feels.
