Jan. 13, 1998 Contacts: Jay Hirsh or Colleen McClung (804) 982-5608 STUDY FINDS COCAINE PROMPTS SIMILAR RESPONSES IN FRUIT FLIES AND HUMANS University of Virginia biologists Jay Hirsh and Colleen McClung have spent a year giving cocaine to fruit flies and then watching what happens. The results? The flies were affected much like rodents -- or humans, for that matter. That is significant for researchers seeking to understand the genetics of behavioral, and perhaps even psychological, responses to cocaine in humans. Hirsh, a biology professor, and McClung, a U.Va. doctoral student, describe the findings of their National Institutes of Health-sponsored research in the cover story of the Jan. 15 issue of Current Biology. Much is already known about the genetics of the frequently studied fruit flies, so it should be easier to isolate the genes involved in their responses to cocaine. That in turn could make it easier to clone the corresponding genes in the higher vertebrates. "These results suggest that ... this genetically tractable animal can be used as a new model system to help determine the biological mechanisms underlying these processes," Hirsh said. Among their observations is that the fruit flies (Drosophila melanogaster) become sensitized to low-dose, intermittent exposures to cocaine. "Sensitization" is a phenomenom, previously seen in higher vertebrates, in which repeated exposures to the same doses of cocaine elicit greater and greater motor responses. For other drugs, such as alcohol or opiates, the opposite is generally true: it takes greater and greater amounts to induce the same biological responses. Sensitization is thought to contribute to the psychoses that occur in long-term cocaine addicts. The fruit flies also showed varied responses to increasing doses of cocaine. At the lowest doses, the flies moved less, spending most of their time grooming themselves. As the dosage increased, the flies became much more active, exhibiting random, meandering and ultimately more frenetic movement, some wandering in seemingly aimless circles. At the highest doses, the flies suffered from tremors and paralysis, and in some cases died. Rodents also show increased reflexive motor activity -- chewing, scratching, grooming and locomotion -- with increasing doses of cocaine, Hirsh and McClung said, indicating that the same type of genes and neural processes are probably at work in both fruit flies and higher vertebrates. "We really don't understand the basic biology of the changes in response to the differences in doses or to repeated doses," Hirsh said. "Basically, we want to find the genes involved," McClung added. The researchers also refined their methods of studying the responses. In the Hirsh lab's previous studies of the behavioral responses of Drosophila melanogaster, they removed the flies' heads and administered stimulants directly to the exposed nerve cords. Amazingly, the flies can live for up to three days without their heads, Hirsh said. In studying fruit flies' response to cocaine, Hirsh and McClung administered the drug differently: basically, they gave the flies tiny amounts of crack cocaine as an aerosol. The process involves mixing the cocaine with ethanol, then allowing the ethanol to evaporate on a filament, leaving tiny crystals of crack. The filament is placed inside a sealed test tube with several fruit flies, then heated, releasing the drug in a vapor form, which is absorbed by the flies. Their flies were then videotaped to allow analysis of the responses. The government-supplied cocaine is carefully monitored. The researchers' work is supported by the National Institute on Drug Abuse and the National Institute of General Medicine Sciences, both agencies of the National Institutes of Health. The research requires very small quantities of the drug, Hirsh said. A year's supply only amounts to about 15 percent of what is used in one day by a human addict. "There is not a lot of cocaine stored in the Hirsh lab," he said. ### For more information, contact Dan Heuchert of the University News Office, (804) 924-7676, or via e-mail at dnh6n@virginia.edu. Hirsh's website is located at http://minerva.acc.virginia.edu/~biology/Fac/Hirsh.html Journalists may obtain the journal article from Current Biology at http://biomednet.com/cbiology/cubsamp2.htm. Michael Sesma, scientific review administrator at the National Institute of General Medical Sciences, NIH, is available for comment at (301) 594-2048, or via e-mail at sesmam@nigms.nih.gov Television reporters should call our TV News Office at (804) 924-7550. U.Va. news online: http://www.virginia.edu/topnews/