Fixing Drug-Addled Brains

MIAMI BEACH, FLORIDA--Scientists have restored the short-term memory of monkeys whose brains were damaged by amphetamines. The finding, presented here today at the Society for Neuroscience's annual meeting, raises hopes of finding ways to reverse the long-term side effects of amphetamine abuse in people.

Amphetamine, or "speed," can trigger bouts of schizophrenia-like psychosis complete with hallucinations, paralysis, and paranoia. Because the long-term effects of a speed habit on people aren't well understood, psychologists Stacey Ann Castner and Patricia Goldman-Rakic of Yale University have been investigating how the drug scrambles primate brains. They gave three monkeys daily doses for 6 weeks, in an experiment that began about 3 years ago.

While drugged, the animals couldn't perform many so-called working memory tasks, such as remembering the location of a hidden food pellet or learning which of two shapes is a clue for finding food. Even after being clean for as long as 2 years, the monkeys still had not recovered memory capacity, failing to learn food-finding skills that healthy monkeys master in days.

The researchers suspected that amphetamine abuse permanently jacks up levels of the neurotransmitter dopamine in the frontal lobes, a brain region necessary for working memory. To find out, the duo injected two monkeys recovering from the years-ago amphetamine habit with a compound that blocks dopamine action. One monkey improved almost immediately: Within a few days, she could find hidden food for the first time in years. The other monkey improved steadily, but more slowly. The third monkey is still getting the treatment. Both monkeys received the compound, a dopamine receptor antagonist, for just a few weeks, but the benefits persisted--6 months after going off the drug, the two monkeys continue to perform well on working memory tests that had stymied them in the past.

"This is so surprising," says psychologist Tim Schallert of the University of Texas, Austin. It's unclear exactly what the dopamine antagonist is fixing, he says, but it could be reviving either the motivation or attention crippled by amphetamines. Whatever the mechanism, he says, "the implications for [former addicts] are broad and very interesting."

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