Calorie kick: desire for sweets not only a matter of taste.

Brains love cakes and cookies and Krispy Kremes, and not just for their taste. Calories feel good too.

Chemical fireworks in the brain's reward system explode in response to calories, independent of flavor, suggests a new study of mice reported in the March 27 Neuron.

Even when researchers eliminated mice's ability to taste food or liquid, the mice consistently chose sugary water over the diet version. The mice were also prevented from smelling or orally sensing texture in the study, by researchers from Duke University in Durham, N.C., and the University of Porto in Portugal.

"This is a very exciting new element in how you get addicted to food," says Tamas Horvath at Yale University School of Medicine. "It doesn't even matter how it tastes."

The brains of the mice without taste receptors responded to real calories instead of low-cal sweeteners, as well. Sugar consumption increased pleasure-inducing dopamine levels in the brain within an hour in taste-challenged mice, while sucralose, better known by its trade name, Splenda, did not. Dopamine, a chemical messenger in the brain, mediates internal rewards and is involved in an addict's drug-seeking behavior. Recently dopamine has been implicated in driving overeaters to binge. But the new work shows that the pleasure doesn't come from taste alone.

When normal mice ate either sugar or artificial sweetener, dopamine levels increased, as expected. But when mice had no ability to taste, only the sugar raised dopamine levels. "The animals' reward processing systems were sensitive to changes in metabolism, not just flavor," explains Ivan E. de Araujo, who led the study while at Duke, but is now at the John B. Pierce Laboratory in New Haven, Conn. "This is a new system."

At the moment, researchers don't know what metabolic cues tip off the brain's reward system. Calorie-rich foods increase blood glucose levels, insulin levels, and other hormones in addition to impacting the gastrointestinal tract. Those signals communicate "hungry" or "stuffed" to the hypothalamus, a part of the brain involved in regulating heat and energy. De Araujo's team observed an apparent calorie effect on activity in the nucleus accumbens, a brain structure involved with reward delivery.

"It looks like caloric load itself can evolve hedonic behavior," Horvath says. The system originated before grocery stores did. When food was harder to find, he says, the brain evolved a mechanism to compel the body to gobble up energy-dense fare.

A reward system that can't be fooled by fake calories may be what trips up dieters. "If someone tries to drink diet soda or eat diet ice cream, they might still have a need to compensate later with calories from other sources," says de Araujo.