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Researchers find how one genetic variation may leave some people vulnerable to addiction

COLUMBUS, Ohio Scientists have learned how a genetic variation long suspected in making some people susceptible to alcoholism and narcotic drug addiction actually does so.

In laboratory studies, this variation greatly reduced the amount of protein that the DNA in a cell produced.

It's the difference in protein expression that may make receptors on certain brain cells much more vulnerable to the effects of addictive drugs, said Wolfgang Sadee, the study's lead author, professor and chair of pharmacology and director of the pharmacogenomics program at Ohio State University. These particular receptors, called mu opioid receptors, serve as a molecular docking station for narcotic drugs and alcohol.

Until now it wasn't clear exactly what about this genetic variation, called A118G, would increase a person's chances of developing a drug addiction. (A118G is a variation in what researchers call the mu opioid receptor gene.)

While Sadee and his team didn't look at the interaction between narcotics and the mu opioid receptor, they suspect that differences in protein production may leave brain cells with these receptors more open to the effects of drugs.

"The real significance of this work is that one day, we may be able to tailor treatments for addiction based on how a person's genes behave," said Sadee, who is also chair of pharmacology at Ohio State .

The study appears in the current issue of the Journal of Biological Chemistry.

The researchers studied brain tissue samples taken from the cerebral cortex and the pons of human cadavers. The pons is a cluster of nerve fibers on the front of the brainstem, and it's responsible for relaying sensory messages from the spinal cord to the cerebellum. The cerebral cortex is a thin layer of tissue that covers the surface of the cerebral hemisphere; it is responsible for processes such as thought, memory, motor function and social abilities.

The researchers studied these
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Contact: Wolfgang Sadee
sadee-1@medctr.osu.edu
614-292-1597
Ohio State University
26-Sep-2005


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