Two geneticists have found that fruit flies respond in the same way to "crack" cocaine as do other animals, including humans. Because humans and fruit flies use many similar biochemical pathways, this discovery suggests that the flies may help scientists unravel the molecular basis of cocaine addiction in people. It may also lay the foundation for highly specific drugs to treat cocaine addiction.
The research, performed by Dr. Jay Hirsh and Colleen McClung of the University of Virginia in Charlottesville, grew out of the group's long-term genetic studies on brain receptors and neurotransmitters--such as dopamine and serotonin--involved in learning, memory, and motor function. Their current findings are featured in a cover story in the January 15 issue of Current Biology.
Cocaine is one of the most powerfully addictive street drugs. Extensive studies on rodents and monkeys have provided little information about the molecular processes that underlie cocaine's behavioral and addictive effects. Using fruit flies in such studies offers several advantages. The genetics of the flies have been intensively studied for 80 years, providing researchers with a rich information base from which to devise and interpret experiments. Not insignificantly, research on flies is cheaper, easier, and faster than similar studies on mammals.
The flies, formally called Drosophila melanogaster, reacted in striking and reproducible ways in response to different levels of cocaine. They also became "sensitized" to the drug, a physiological process thought to be involved in human drug addiction.
"This study shows that the nature of the changes in the Drosophila brain and nervous system in response to cocaine are probably very similar to those that occur in the human brain. This gives us a new tool to learn more about brain receptors and neurotransmitters, and also to better understand the genetic and physiological basis of cocaine addiction," said Dr. Michael Sesma of the Division of Genetics and Developmental Biology at the National Institute of General Medical Sciences (NIGMS), which supported the research.
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.
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 biomedical research. Please fax clips to NIGMS at (301) 402-0224. The cocaine used in this study was supplied by another NIH component, the National Institute on Drug Abuse. This release will be available online at http://www.nih.gov/nigms/news/releases/cocaine.html after the embargo date.
Journalists may obtain the journal article from Current Biology at http://biomednet.com/cbiology/cubsamp2.htm.
McClung C and Hirsh J. Stereotypic Behavioral Responses to Free-Base Cocaine and the Development of Behavioral Sensitization in Drosophila. Current Biology 1998; 8:109-112.
Dr. Jay Hirsh, professor
Colleen McClung, graduate student
Department of Biology
University of Virginia, Charlottesville
University of Virginia News Officer
For scientific perspective on this research, call the NIGMS Public Information Office at (301) 496-7301 to interview Dr. Michael Sesma, program director, Division of Genetics and Developmental Biology, NIGMS.