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Animals resistant to drunken behavior offer clues to alcoholism's roots

Animals with a remarkable ability to hold their liquor may point the way toward the genetic underpinnings of alcohol addiction, two separate research teams reported in the October 6, 2006 issue of the journal Cell. Earlier studies have shown that people with a greater tolerance for alcohol have a greater risk of becoming alcoholics, according to the researchers.

In one study, researchers at the Fondazione Istituto FIRC di Oncologia Molecolare in Italy found that mice lacking a gene that influences the cellular "skeleton" become less susceptible to the intoxicating effects of alcohol. The animals consequently drink more ethanol than the average mouse, they reported. They further showed that the mutant animals' neurons became less sensitive to "remodeling" of the cytoskeleton that otherwise follows ethanol exposure.

In the second paper, a team of researchers led by Adrian Rothenfluh and Ulrike Heberlein at the University of California, San Francisco characterized flies that carried a mutation rendering them invulnerable to drunken behavior. They discovered that the ethanol-resistant flies failed to produce a regulatory protein underlying the sedative effects of alcohol. The lacking protein is one of three encoded by a single gene and is also suspected to influence the cytoskeleton of neurons, though indirectly.

"Most researchers in the alcohol field have focused on cell surface receptors--with little attention to the role of the cytoskeleton," said Ulrike Heberlein at UCSF, who is an author on both papers. "Now, these two papers have, through very different means, come to highlight a possible role of the actin cytoskeleton in behavioral responses to ethanol."

Cytoskeletal defects may have the ability to simultaneously change the dynamics of multiple receptors, she said. "These animals are tremendously resistant to alcohol. There seems to be something very central about the observed changes to their behavior."

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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
5-Oct-2006


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