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Updated 10:00 AM November 13, 2006
 

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  Research
Tiny worm provides model for the genetics of nicotine dependence

The unassuming C. elegans nematode worm, a 1-millimeter workhorse of the genetics lab, has the same genetic susceptibility to nicotine dependence as a human being, according to University researchers.
The microscopic C. Elegans, like humans, is susceptible to nicotine and its effects. (Courtesy X.Z. Shawn Xu)

This finding should allow researchers to better understand how nicotine dependence works, and perhaps devise new ways to block the craving that keeps humans smoking cigarettes. Dependence on nicotine drives many of the most preventable causes of death in the U.S. and is a worldwide health problem.

A team lead by X.Z. Shawn Xu, assistant research professor at the Life Sciences Institute and assistant professor of physiology at the Medical School, has completed a series of experiments which establish that C. elegans can get hooked on nicotine. Like humans, the nicotine-sensitive worms showed acute responses to nicotine exposure, as well as tolerance, sensitization and withdrawal.

"It turns out that worms exhibited behavioral responses to nicotine that parallel those observed in mammals," said Xu (pronounced Shoo). "But it is much easier to identify novel functions of a gene in worms."

Xu and his team found that the genes known to underlie nicotine dependence in mammals also are present in the worms. Having established worms as a model, the Xu team then tried to identify new genes important for nicotine dependence. They found for the first time that TRP channel genes, which enable cells to respond to various external stimuli, are a part of the nicotine response.

In fact, when they knocked the TRP gene out of some nematodes, the animals no longer responded to nicotine exposures. But when a new generation of worms had that missing gene replaced by a human version of the TRP gene, the worms returned to being nicotine-sensitive.

"This demonstrates that human TRP genes have the capacity to mediate nicotine dependence in worms, raising the possibility that these genes may be important for nicotine dependence in humans," Xu said.

It also makes TRP genes a potential target for the development of drugs to treat tobacco addiction, and the worms can help in that research. C. elegans also can be used to find other unknown genes critical for nicotine dependence.

The paper "A C. elegans Model of Nicotine-dependent Behavior: Regulation by TRP-Family Channels" appeared online in Cell on Nov. 3 and in the upcoming print version. For more information go to www.lsi.umich.edu and lsi.umich.edu/labs/xz-xu.

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