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University of Texas at Austin researchers identify drug-tolerance mechanism in flies

AUSTIN, Texas--A protein found on the surface of nerve cells makes fruit flies tolerant to a drug after just a single, brief exposure, which may reveal ways to address this early step toward addiction in humans.

Neuroscientist Nigel Atkinson at The University of Texas at Austin and his laboratory determined this by studying the response of fruit flies (Drosophila) to a 15-minute exposure to benzyl alcohol coated on the inner walls of test tubes. Flies that had had one previous exposure to the organic solvent recovered more quickly from being knocked out by the drug than flies that were first-timers. The flies that developed tolerance also had increased activity of the slo gene. The gene produces the surface protein, which helps stimulate signaling between nerve cells in the brain.

Genetically modified flies that lacked the slo gene failed to develop tolerance, while flies modified to have increased slo activity were more drug resistant than normal, providing added proof of the gene's importance for tolerance.

Because the human slo gene is almost identical to the one in fruit flies, Atkinson said, "If we could describe the series of steps involved in changing slo gene expression, then all the components involved in producing that change could become potential targets for anti-addiction drugs."

The findings will be published online the week of Monday, Nov. 29, by the Proceedings of the National Academy of Sciences.

Benzyl alcohol (BA) is usually used as an anesthetic. Although few people seek it as a drug, the same behavioral and genetic effects were found when flies were exposed to the addictive chemical in glue or other addictive organic solvents. Initially, flies placed inside BA-laden test tubes began moving quickly and climbing the walls. Within minutes, this excited phase ended and they started falling off the walls and stumbling, before passing out.

"They start trippin
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Contact: Barbra Rodriguez
brodriguez@mail.utexas.edu
512-297-3049
University of Texas at Austin
29-Nov-2004


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