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My mother can’t drink anything but decaf coffee after lunch or she’ll be awake all night long. I, on the other hand, can easily put away a Red-Eye Special at the Java Hut (that’s three shots of espresso in a large coffee, for the uninitiated) at 9 in the evening and be blissfully asleep by midnight. What makes us so different? The answer could be in the same gene that may hold information that will cure Parkinson’s disease and schizophrenia, and reduce addiction to drugs like cocaine, nicotine and… caffeine.
DARPP-32 is a protein expressed by a gene in the brain of a mouse. There is a similar gene in the human brain. It seems to act as a sort of regulator for other proteins and chemicals that affect things like mood, alertness, cognitive functioning and sleep. One of the things it does is trigger the brain to release another chemical called adenosine. When your brain gets over-stimulated, adenosine levels build up, and eventually trigger drowsiness. Caffeine – along with other stimulant drugs like cocaine and nicotine – seem to block the production of adenosine, so your brain just keeps on going and going and going like the Energizer bunny.
Interestingly, back in 2002 researchers in Sweden used mice that were genetically engineered with non-fucntioning DARPP-32 genes in a study on the effects of caffeine. They fed caffeine to those mice and to mice with DARPP-32 genes. The mice with normal functioning were affected for a far longer time by the caffeine than those whose DARPP-32 genes were blocked. Dr. Jean Marie Vaugeois at the University of Rouen speculated that coffee has such a powerful and long-lasting effect on many people because it binds to and blocks brain nerve cell receptors that play a role in calming down over-stimulation.
Normally, over-stimulation is controlled by a number of proteins that stop DARPP-32 from working, effectively killing the caffeine buzz, but when you combine caffeine with DARPP-32 (which is also the name of the protein that the gene expresses), it subdues production of those proteins and chemicals, creating a circular effect that keeps that buzz going for hours.
The genetically engineered mice needed twice as much caffeine to get the same effect as those with normally functioning DARPP-32 in their brains. These same mice have been used in research on the mechanism of addiction to cocaine, where researchers found that the genetically engineered mice did not work harder for cocaine-laced rewards, suggesting that the mechanism that addicts people to cocaine and other stimulants may be linked to the actions of DARPP-32.
The research on the effect of caffeine on brain chemicals continues. In 2005, researchers at UT Southwestern University found that adenosine, one of the chemicals blocked by caffeine, seems to act as a ‘soother’ when the brain has been functioning at highly stimulated levels. In a circular sort of reaction, prolonged neural activity in the brain triggers the release of adenosine, which triggers drowsiness and sleep. When you add caffeine to the brain, the production of adenosine is blocked so there’s no ‘mom’ to tell the brain cells to go to sleep for a while.
Sleep disruption is also a major symptom in disorders like depression, schizophrenia and post-traumatic stress disorder, so research into the way that caffeine affects the chemicals in the brain could hold the key to information that will help discover the root causes of those disorders and many others.