To deliver cocaine to the flies, the researchers applied a droplet of "crack" cocaine dissolved in alcohol to a wire filament. After allowing the alcohol to evaporate, they placed the wire in a tiny glass tube containing several flies. As the wire was heated by an electric current, "crack" was released in a cloud of smoke that was absorbed by the flies.

In response to low doses of cocaine, the flies continuously groomed themselves. With higher cocaine levels, they walked backward, sideways, and in circles. At the highest doses, the flies developed tremors, paralysis, or even died.

When flies were repeatedly exposed to cocaine given at intervals, they exhibited more severe responses. Such sensitization, or "reverse tolerance," also occurs in rodents and humans and may underlie the paranoia and pyschosis seen in long-time cocaine addicts. It is the opposite of what occurs in response to other drugs, such as opiates and alcohol, for which increasingly larger doses are required to induce the same effects.

Dr. Hirsh and Ms. McClung are already beginning to examine the genetic basis of cocaine sensitization in fruit flies. One method they are using is to select from vast collections of mutant flies those that respond differently to cocaine. By comparing the genes of these flies with those of normal flies, they hope to reveal the genetic and biochemical pathways involved in cocaine-induced behavior and addiction. These insights may lead to better treatments for cocaine addiction.

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Please mention support for this work from the National Institute of General Medical Sciences (NIGMS), a component of the National Institutes of Health that supports basic biomedica
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Contact: Alisa Zapp Machalek
alisa.zapp@nih.gov
(301) 496-7301
NIH/National Institute of General Medical Sciences
13-Jan-1998