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Memory may draw addicts back to cocaine

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10:36am, May 9, 2001
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Nostalgia may be a recovering drug addict's worst enemy. A memory center of the brain acts as an ignition switch for relapse into cocaine addiction, scientists suggest in the May 11 Science.

The researchers electrically stimulated the hippocampus in the brains of formerly drug-addicted rats. The treatment reignited powerful cravings for cocaine.

"It is the first time anyone has ever been able to stimulate relapse by [electrically] stimulating a brain circuit," says coauthor Eliot L. Gardner of the National Institute on Drug Abuse in Baltimore.

The finding suggests that the hippocampus, an area that participates in the recall of memories, and a chemical it releases play important roles in addiction relapses, report Gardner, Stanislav R. Vorel of the Albert Einstein College of Medicine in New York City, and their colleagues. The study could lead in 10 to 15 years to novel drugs to stem the cravings that lead to relapses of addiction, Gardner says.

People grapple with cravings long after escaping chemical dependency. For addicts, even simple reminders of past drug use, such as the sight of a certain street corner, can trigger cravings that lead to renewed abuse and drug dependence. Results from laboratory studies indicate that animals return to drug-seeking behavior when they experience stress and other stimuli similar to those that send people back to drugs.

For many years, scientists have associated the hippocampus with drug-experience memories, but research hadn't revealed any physiological pathway leading from memory to relapse, says Vorel. The hippocampus has been linked to the reward pathways of addiction, which lead to the release of the neurotransmitter dopamine and the pleasurable effects of drugs. However, brain imaging of people who say they are experiencing cravings showed no activation in the hippocampus.

In their experiment, Vorel, Gardner, and their colleagues trained rats to press a lever to receive a dose of cocaine directly into the bloodstream. After the researchers cut off the rats' cocaine supply, the lever-pressing behavior gradually ceased. This results from dwindling cravings, the researchers say.

The scientists next applied a specific pattern of electrical pulses to the rat's hippocampus. In response, the animals began pressing the lever again. A drug that blocks glutamate, a signal chemical released by the hippocampus, prevented the behavior. Other types of pulses and the stimulation of other memory regions and the reward pathway did not lead to lever pushing.

The new work points to glutamate as the mediator of the well-known process in which hippocampal activity can cause the release of dopamine by another part of the brain, says Vorel. This neurochemical detail links the relapse and reward pathways, he says, so dopamine must play a role in relapses.

He speculates that dopamine acts as a reminder of past rewards rather than just as a pleasure inducer.

Dopamine's role as stimulus for craving surprises those researchers who thought of the neurotransmitter as satisfying an addict's desire, says Kent Berridge of the University of Michigan in Ann Arbor. "To show that it's the opposite is a major piece of interesting research."

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