Persistent Memories of Cocaine

By Jason Socrates Bardi

Several years ago, a former drug addict confided to a group of recovering drug addicts, their families, and their friends at a 12-step program meeting in the Midwest that he could no longer eat fast food.

In the three years that he had been clean, he said, every fast food restaurant he entered made him crave drugs. In the day that he was using, he would go to these restaurants, lock himself in the bathroom, and get high. Any time he was in a fast food restaurant, the memory of those sessions would be enough to trigger cravings.

This addict's story is common enough, and the phenomenon it illustrates is a familiar one—addicts suffer from prolonged vulnerability to relapse, and the motivation to relapse arises not only because of the physical dependence to the substance itself but because of the contributions of memories and associations, like a fast food bathroom, that the addict links to drug taking.

Unfortunately, these environmental and learning factors may be relevant not only for serious addicts who have a history of abuse but also for users who have not habituated themselves to a drug.

Recent experiments at The Scripps Research Institute suggest association-driven desire for cocaine can persist for long periods of time even after a single dose of the drug.

These experiments were conducted by Associate Professor Friedbert Weiss and his colleagues, Senior Research Associate Remi Martin-Fardon and Associate Professor Pietro Sanna in the Department of Neuropharmacology at Scripps Research and Roberto Ciccocioppo, who is an Assistant Professor in the Department of Pharmacological Sciences and Experimental Medicine at the University of Cagliary in Italy and a visiting investigator at Scripps Research.

Powerful Conditioning

The results, which are being published in next month's issue of the journal Nature Neuroscience, are the fortuitous by-product of other studies.

Weiss and his colleagues are interested, generally, in understanding the brain architectures, the mechanisms, and the neurochemistry that drive addiction and relapse. Lately, they have been asking specifically why drug craving persists for long periods of time after an addict stops taking a drug.

One of the issues they have focused on is the conditioning that takes place whereby an addict associates a drug with a particular environment. These sorts of studies normally require repeated pairing of a drug with some environmental cue (like a particular noise) in order to determine which parts of the brain are involved in making the association.

Recently Ciccocioppo, Martin-Fardon, and Weiss discovered that this conditioning is powerful enough to occur following even a single exposure, and laboratory rodents have shown conditioned motor locomotor activity to the environment in which they previously received a single injection of cocaine.

The scientists wanted to gauge how long this effect would last, so they exposed their laboratory rodents to a single opportunity to intravenously self-administer cocaine and then tested them every three months. For up to one year, they observed a strong conditioned desire to again consume cocaine.

The same effect was not observed when the laboratory rodents were given sweetened condensed milk—a control substance that is highly desirous. The sweetened condensed milk didn't engender the same addictive effect.

The mental processes involved in drug-related learning, says Weiss, appear differently than those that go on in the normal learning process. Drug-related experiences leave a much stronger and longer-lasting trace than do stimuli conditioned to conventional rewards.

The fallout of this study is likely to be significant, since these learning processes are important both for development of dependence and for relapse. At the moment, Weiss and his colleagues are investigating which brain mechanisms control this differential learning.

To read the article "Stimuli associated with a single cocaine experience elicit longlasting cocaine-seeking" by Roberto Ciccocioppo1, Rémi Martin-Fardon, and Friedbert Weiss see the May 2004 issue of Nature Neuroscience or go to: http://dx.doi.org/10.1038/nn1219

Send comments to: jasonb@scripps.edu

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