Scientists have located a gene for a brain protein that ordinarily allows moments of pleasure but lies defenseless in the pathway of cocaine, letting brain cells have a field day spewing out the pleasurable feelings drug users describe as a "high."
The discovery is considered a leap in understanding the biology of how a major addicting drug works.
"This is a milestone in terms of our understanding of the brain and its relation to drug dependence," said Dr. Roy Pickens, director of the Addiction Research Center of the National Institute on Drug Abuse (NIDA).
"The ultimate outcome from this may be a better understanding of why people become dependent on cocaine in the first place. It might also allow us to develop better medications for the treatment of cocaine dependence," he said.
Two groups of scientists report finding identical protein transporters of the naturally occurring chemical dopamine in brain cells in today's issue of Science. Dopamine is a substance occurring in one part of the brain that lets people enjoy good food, good drink and good sex. In another region of the brain, dopamine plays a role in movement and is linked to Parkinson's dTC disease, a condition characterized by involuntary jerky movements, among other symptoms.
Cells communicate with one another by spitting out their messages. When the brain decides to let us feel life's normal daily pleasures, it shoots dopamine out to the next nearby cell. After the dopamine reaches the second cell, a protein transporter pulls the surplus dopamine back inside the first cell. The transporter plays the role of a good mother or a good bartender -- saying that's enough, no more, don't overdo.
But cocaine appears to paralyze the transporter, and with the gatekeeper out of the way, the nerve cell goes hog wild shooting out dopamine.
Cocaine is thus not itself a drug that causes pleasure: It is a substance that paralyzes a gatekeeper, allowing the brain's own naturally occurring chemicals to overproduce. When levels of cocaine eventually diminish in the drug user's body, the transporter starts acting once again as a gatekeeper.
One scientific group that discovered the transporter was led by Dr. George Uhl, chief of the molecular neurobiology lab at NIDA's Addiction Research Center in Baltimore. He is also an associate professor of neurology and neuroscience at Johns Hopkins.
"For the first time, we can understand the molecular mechanism by which cocaine works," Dr. Uhl said.
Next, he and other scientists will try to find some small region of the transporter essential for binding with cocaine but not essential for moving the brain's dopamine.
This could lead to "development of drugs to block cocaine action," he said. "Such drugs could block the acute effects of cocaine and might even reduce cocaine craving."
Dr. Michael Kuhar, a Hopkins professor who is also chief of the neuroscience branch at NIDA's Addiction Research Center and a co-author of the Science paper with Dr. Uhl, previously discovered that cocaine acts on the dopamine transporter. The Science paper details the cloning of the gene for the protein transporter in the rat brain, the first important step toward locating the similar gene in the human brain, which Dr. Uhl's lab has now identified.