More than four million people die from smoking-related causes each year, making nicotine addiction a leading cause of preventable mortality worldwide. But nicotine's highly addictive nature makes kicking the smoking habit very difficult. A report published today in the journal Science identifies brain receptors in mice that may help explain why it's so hard to quit, and help scientists develop new drugs to help smokers butt out.

Receptors embedded in the surface of neurons allow compounds such as nicotine to act on brain cells. Researchers had previously identified so-called nicotinic acetylcholine receptors as important in cigarette addiction. Henry A. Lester of the California Institute of Technology and his colleagues created genetically engineered mice that had alterations in these receptors. They found that animals with a mutation in the ¿alpha4¿ subsection were particularly sensitive to nicotine's effects. Mice with the alpha4 mutation showed signs of addiction at lower doses than did normal mice and, once exposed to the chemical, the altered neurons responded more strongly to large doses of it than regular neurons did.

The new findings offer insight into how the chemical exerts its addictive power, but the mechanism of how nicotine binds to the receptors remains unclear. ¿It's a complicated pathway that still must be broken down into individual steps before we can understand it fully," Lester says, "but I personally believe that nicotine addiction will be among the first addictions to be solved, because we already have so many tools to study it."

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