Repeated Exposure To Cocaine Alters Brain Structure

Robinson described his finding at the Fifth Annual Wisconsin Symposium on Emotion, held April 23-24.

"Repeated exposure to cocaine results in persisting brain changes that we believe contribute to addiction and the risk of relapse," he said.

Robinson and his colleague, Dr. Bryan Kolb of the University of Lethbridge, reported two years ago that rats exposed over time to amphetamines displayed abnormally elongated and densely packed dendrites, the branched portions of nerve cells that receive the majority of signals from other neurons. Such structural changes probably enhance synaptic connectivity, improving the efficiency with which messages are transmitted between nerve cells, he said.

The scientists also saw that drug-induced changes were localized in the nucleus accumbens and the prefrontal cortex, brain regions where processes involving reward, learning and memory normally take place.

In recent experiments with cocaine, Robinson and Kolb observed similar dendritic alterations in the same brain regions in rats. The same alterations were seen in animals that were given cocaine by experimenters and those that were allowed to self-administer the drug intravenously. The changes were remarkably persistent, well outlasting the acute effects of the drug and withdrawal from it.

"We propose that the increased synaptic connectivity resulting from repeated exposure to cocaine and amphetamines produces a hypersensitivity, or neural sensitization, in these areas of the brain, stimulating animals and people to constantly work harder for the drug," he said. "This neural sensitization stands in contrast to the better known phenomenon of drug tolerance, which is reduced responsiveness."

Circumstances that surround drug taking--environmental cues--exert a powerful influence over sensitization, he added. His studies have shown that sensitization is diminished when drugs are administered "out of context." Research under way in UW Medical School's psychiatry department is yielding related results. Dr. Ann Kelley is studying rats that become sensitized to repeated morphine exposure and show enhanced activity even when they are presented only cues associated with the drug.

Kelley and graduate student Brock Schroeder have seen that the cues alone can trigger neuronal activity-expression of the nuclear protein c-fos--in the nucleus accumbens, the prefrontal cortex and other brain regions associated with learning and emotion.

"The fact that classical conditioning may produce alterations in neuronal gene expression suggests that the craving and relapse associated with addiction may have molecular underpinnings," she said.

The topic of this year's Wisconsin Symposium on Emotion is "Affect and Plasticity: Neural Mechanisms Underlying Emotional Change." More than 300 participants have gathered to discuss the latest research on brain changes that occur in response to various life experiences.