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New clues about what gives caffeine its kick

New clues about what gives caffeine its kick

By Bill Davis
Special to

(CNN) -- A cup of coffee can keep you awake for a long time, and scientists think they know why. Researchers have discovered a new function of a protein that intensifies the caffeine kick.

In a study published in Wednesday's issue of the journal Nature, researchers describe a new role for the protein DARPP-32. This protein is found in mouse brains, and a similar version is found in humans. This work explains how coffee gives us a buzz.

When a mouse drinks coffee or when a scientist injects it with caffeine, some of the caffeine ends up in the mouse's brain. There the caffeine stimulates the mouse's nerves. The effects are familiar--the mouse gets jittery, its heart rate increases, and it runs around.

Once the effects from caffeine get started, DARPP-32 keeps them going.

"DARPP-32 acts as an amplification system able to sustain the effects of caffeine," said Gilberto Fisone, a researcher at the Karolinska Institute in Sweden and co-author of the report.

A small signal started by caffeine gets turned into a large signal that can last for a long time, in what scientists call a positive-feedback mechanism. A little bit of coffee can start the reaction and DARPP-32 keeps it going.

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"It makes caffeine longer lasting," according to Fisone.

One way scientists learned about DARPP-32 was to make a mutant mouse that didn't have this protein. Scientists gave this mouse caffeine -- the equivalent of three cups of coffee for people -- and saw that the caffeine had no effect on the mouse. There was no DARPP-32 in the mouse to amplify the signal from caffeine and so the mouse behaved normally.

Scientists found that if they loaded the mouse with caffeine -- the equivalent of giving a person six cups of coffee at once -- the mouse acted like a normal mouse given a small dose of caffeine. In this case, they gave the mouse so much caffeine that the original signal didn't need any amplification to have an effect on the mouse.

What scientists found in mice may also apply to humans; there is a human protein that is very similar to mouse DARPP-32. DARPP-32 is involved in the brain's responses to amphetamines and cocaine, and it may play a role in addictive behavior or other neurological disorders.

"DARPP-32 may be a common denominator for a psychostimulant effect," said Fisone.


• Nature

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