Brain Pleasure Pathway Responds to Calorie-Rich Foods, Not Just Sugar Flavor
DURHAM, N.C. – Researchers at Duke University Medical Center
have discovered that the brain can respond to the calorie
content of food, even in the absence of taste.
Their findings about the brain's dopamine-reward system may
help shed light on why many people who drink diet sodas still
gain weight. A mismatch between artificially sweet taste and
zero calorie content may lead to some kind of rebound eating
that may in part be explained by these results: the brain is
wired to respond to both calorie content and sweetness.
For years, scientists have known that when mammals,
including humans, taste sweet foods, dopamine levels increase
in the ventral striatum, a brain region related to reward and
reinforcement. The neural pathways have been well established
for palatability (the power of a food to make one eat it
spontaneously and with gusto) as food is being eaten. With this
set of experiments, the Duke team studied the brain's response
to food after it was ingested.
Using mice that lacked sweet-taste receptors as a model, the
researchers studied behavior as well as neural responses in the
study published in the journal Neuron on March 27.
Mice that were unable to taste sweetness, either in real
sugar (sucrose) or artificial sweeteners (sucralose), developed
preferences for real sugar but not non-caloric sweetener. Mice
with normal taste receptors also developed the same type of
"The fact that sweet-blind animals are conditioned by
sucrose only, demonstrates that they can detect this sugar
because of its caloric content and adequately modify their
behavior to obtain this reward, independent of taste input,"
said researcher Albino Oliveira-Maia, of the Duke Department of
Neurobiology and the University of Porto in Portugal.
To reach this conclusion, the researchers first confirmed
that one set of mice did not exhibit a taste
motivated-preference for sucrose. Normal mice naturally
preferred various concentrations of sugar solutions to water,
but mice without functional sweet taste pathways did not show
The scientists then explored preference in mice that were
both hungry and thirsty. During conditioning sessions with two
bottles, both the normal mice and the taste-impaired mice
consumed more sucrose than water. When conditioning was
complete, preference tests with two bottles of water was
conducted. Both groups of mice preferred the sipper that had
been filled with sucrose during conditioning sessions.
Substituting an artificial sweetener, sucralose, for the
sucrose solution, the scientists ran the conditioning
experiment again and found that while the normal animals
consumed much more of the sucralose solution than water, the
sweet-blind mice consumed about the same amount of both.
Neither group showed a preference for the sucralose sipper
during the test session.
The conclusion: both groups of mice were conditioned by
sucrose, which must have depended on the calories obtained from
The researchers also found significant differences in
dopamine levels during eating, regardless of the ability to
taste food. Normal mice showed a rise in dopamine when they
gobbled the artificial sweetener solution, indicating
palatability even without calories present. Mice without sweet
taste released dopamine only during sucrose intake, even though
they could not distinguish between the taste of water and
sucrose. This confirmed that dopamine can be released in the
ventral striatum by either sweet taste or caloric content.
It may mean that the role of dopamine transmission (the
pleasure principle) in overeating and obesity might not be
restricted to taste alone – dopamine signaling also can
influence behavior by indicating a food's caloric value.
The authors also demonstrated that neurons in the same area
of the brain had significantly higher responses when
taste-impaired mice were consuming sucrose in comparison to
"This suggests that the calorie-dependent release of
dopamine in the ventral striatum has an impact on the response
properties of populations of neurons in the same area," said
Miguel Nicolelis, professor in the Duke Departments of
Neurobiology and Biomedical Engineering and the Center for
Neuroengineering. "Thus, the brain dopamine pathways might also
perform an action we had not previously identified, by
detecting gastrointestinal and metabolic signals."
"The metabolic effect we see may also feed into the same
neuronal pathway that we associate with pleasure," said Marc
Caron, professor in the Duke Department of Cell Biology.
Other researchers included Sidney Simon of the Duke
Departments of Neurobiology and Anesthesiology and the Center
for Neuroengineering; Ivan de Araujo of the Department of
Neurobiology and the Center for Neuroengineering; and Tatyana
Sotnikova and Raul Gainetdinov of the Department of Cell