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Cocaine Addition Linked To Brain Protein

October 25, 1991

WASHINGTON (AP) _ Scientists say they found the gene for an important brain protein involved in cocaine addiction in what may be another step toward a treatment to block the drug’s effect.

Although much more research is needed before such a treatment could be developed, two groups of researchers said, the finding gives them a far better understanding of how cocaine works in the brain.

″This opens up a whole range of new molecular studies that will help us understand how nerves work under normal functioning,″ said Michael Kuhar, a scientist at the National Institute on Drug Abuse and the Johns Hopkins University medical school.

″In addition to that, we’re going to find out something highly specific about what cocaine does, and once we know how cocaine affects the function of this molecule, then we may be able to rationally design some antidote or some blocker, but I would emphasize may,″ Kuhar added.

By understanding the molecular mechanism by which cocaine works, scientists someday may also be able to identify people who may be at high risk for cocaine addiction, said Dr. George Uhl, lead author of the study with Kuhar.

Susan Amara, associate professor at Oregon Health Sciences University and co-author of the other study, said the finding is ″one step in a very complicated pathway″ toward a treatment for cocaine addiction.

″Knowing this and many other steps that will follow, we’ll be able to understand the molecular mechanism involved in addiction, and it will allow us ultimately to intervene″ and break the addiction process, she said.

The studies were to be published Friday in Science, the journal of the American Academy for the Advancement of Science.

Each group of researchers cloned a protein, called a dopamine transporter, and showed its action could be blocked by cocaine.

Some cells communicate by releasing dopamine as a chemical messenger, or dopamine neurotransmitter. Once neurotransmitters have delivered their message, it is the job of the transporters to lock onto the neurotransmitters and take them back to the cell that originated the message.

Cocaine, as well as other drugs such as amphetamines, bind to the transporter, preventing it from shutting down the message stream. This prolonged stimulation results in intense euphoria and increased movement.

Uhl said scientists can now try to split up the protein, separating the parts necessary for cocaine binding from those that transport dopamine. This could pave the way for development of a drug that blocks cocaine’s action but does not affect dopamine uptake, he said.

Amara’s work isolating the gene of the dopamine transporter builds on her earlier work in which she reported the structure of the norepinephrine transporter, which is a target for certain antidepressant drugs.

The norepinephrine transporter is also inhibited by cocaine and amphetamines, but the dopamine transporter is more closely tied to cocaine’s addictive properties, she said.

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