From aversion to obsession: how our brain learns to love coffee, sugar and fat

That first sip of coffee in a person’s life is rarely love at first sip. From an evolutionary perspective, the bitter taste acts as an ancestral warning signal linked to the presence of toxins – a signal that instinctively prompts us to spit it out. And yet, a vast proportion of the world’s population ends up developing a daily craving for that bitterness, just as they fall in love with dark chocolate or combinations rich in fat and sugar. The explanation for this radical shift in preferences lies not in the taste buds, but in a previously little-explored communication pathway between the digestive system and the brain. The dynamics of this transformation are clarified by a study conducted by researchers at the University of California, San Francisco (UCSF), published in the journal Nature.

Until now, the neurobiology of reward has focused on the study of dopamine’s immediate responses – those stimuli triggered in fractions of a second by external factors such as the sight or smell of an appetising dish. Now, however, the team of researchers, led by Zachary Knight, a professor of physiology at UCSF, has identified a second circuit – one that is much more gradual and subtle – regulated by what happens within the body. “We have shown that this slow dopaminergic system is what drives us to learn to love certain foods over time, and we can now see where and how this happens,” explains Knight. The researcher emphasises that whilst our day-to-day awareness of this process is minimal, it is nonetheless crucial. “Once the brain learns to associate the aroma of your favourite blend with the energy boost from caffeine, that coffee suddenly starts to taste much better,” the scientist points out. The process is triggered when the chemical sensors in the gastrointestinal tract detect nutrients such as sugars and fats. The dopaminergic signal does not surge immediately, but builds up as the bolus reaches the intestine and remains active for several minutes. It is precisely this persistence that allows the nervous system to link the taste memory on the tongue with the caloric intake absorbed shortly afterwards.

To isolate the phenomenon and completely rule out the initial role of taste, the researchers administered nutrients in the form of sugar solutions or thick mixtures similar to a milkshake directly into the stomachs of laboratory mice, bypassing the oral cavity, whilst monitoring neural activity. The infusion triggered a robust and prolonged response in the anterior basolateral amygdala, a brain region known as the BLA. Although it was already known that this area releases dopamine, its actual physiological function remained unknown. “We were finally able to see that this dopamine is part of a completely distinct system and begin to understand its role,” comments Knight. The researchers then manipulated the circuit to test its causal link with learning. By artificially blocking the pathway in the BLA, the animals continued to feed normally but lost the ability to recognise that an unfamiliar flavour signalled the arrival of calories. Reversing the paradigm, the scientists artificially stimulated the dopaminergic fibres immediately after allowing the mice to taste a calorie-free flavoured substance. The effect was immediate: the animals learnt to enjoy that artificial flavour, deceived by the stimulation which simulated the presence of real nutrients.

This phenomenon is not limited to rodents. Working with Knight, Yale psychologist Dana Small re-examined data from a previous PET scan study involving thirteen male volunteers who had been given either calorie-containing or diet drinks, finding that dopamine release was specifically concentrated in the left side of the amygdala as soon as the calories reached the gut. Similar results emerged from functional magnetic resonance imaging (fMRI) scans of 38 adults following the ingestion of glucose. In both human and animal models, a curious asymmetry emerged: the left side of the BLA reacts with markedly greater intensity than the right. This is an unexpected anomaly for basic biological functions such as nutrition, which are usually controlled by mirror-image neural networks in the two hemispheres, and it is precisely this imbalance that the San Francisco laboratory is now focusing its investigations on.

Charting this course opens up new avenues for tackling obesity and food addictions. GLP-1 receptor agonists, which have become renowned for their effectiveness in curbing appetite, are also at the centre of the debate. Although they were not the direct focus of this study, Knight hypothesises that these active ingredients may work by dampening the slow-release dopamine triggered by the gut, making food progressively less rewarding. The real clinical breakthrough could lie in the ability to act at the root of food conditioning. “By understanding the pathways linking the detection of nutrients in the gut to learning in the brain, it might become possible to fine-tune these mechanisms to subtly alter our preferences towards different foods,” concludes Knight. It would no longer be simply a matter of suppressing the feeling of hunger, but of rewriting what the palate finds irresistible.