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 Assistant 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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