Drunken Fruit Flies Reveal Molecular Pathway Regulating Sensitivity To Alcohol

came more sensitive, or more inebriated, than their brethren. More importantly, however, when the researchers examined how the amnesiac gene normally functions within the fruit fly's neural system, they determined that it regulates the cyclic AMP (cAMP) pathway, a signal transduction cascade that scientists at the Gallo Center have long known was affected by alcohol through studies in human cells. This discovery fit with a previous finding, namely that amnesiac is believed to encode a molecule that stimulates cAMP production.

The scientists thus deduced that the fruit flies missing the amnesiac gene had reduced cAMP production, and that this action caused greater intoxication. To test their hypothesis, they treated the mutant amnesiac flies with agents that increased cAMP levels and were able to reverse the alcohol sensitivity. The finding made a giant leap from an isolated gene in fruit flies to an entire molecular pathway previously observed in animal and human cell cultures.

"This was an exciting discovery," said Heberlein. "We've known cAMP was involved in the brain's response to alcohol, but we haven't known what role it plays in causing the behavioral effects associated with intoxication. Our study demonstrates that proper regulation of the cAMP signaling pathway is central to establishing ethanol sensitivity in Drosophila."

The finding does not suggest that the amnesiac mutation exists in humans, nor that any one gene affects sensitivity to alcohol in higher animals. The significance, said Heberlein "is that we have found a pathway that modulates the response to alcohol."

"Our next step, she said, "is to identify more genes in fruit flies associated with alcohol behaviors and to see if we can find homologous, or similarly acting, genes in higher organisms, including mice and humans." Ultimately, of course, if these genes do exist in humans the researchers hope to find that they are linked to alcoholic behaviors.

Given how strikingly simi

Contact: Jennifer O'Brien
(415) 476-2557
University of California - San Francisco

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