Molecule may be key to nicotine addiction

A single molecule may be partly to blame for nicotine’s addictive allure, a finding that researchers say could lead to potential therapies to help millions of smokers quit a life-threatening habit.

More than 4 million people around the globe — 440,000 of them Americans — die from smoking-related causes each year. And, the nicotine-laced smoke damages more than just their lungs.

The California researchers not only pinpointed a molecule responsible for nicotine addiction, they also created specialized mice to make it easier to search for other molecules impacted by nicotine addiction.

The research team started by fiddling with a single gene to create mice that were hypersensitive to nicotine. The genetically engineered mice were tripped up by the tiniest exposure to nicotine — a concentration 1/50th of the strength of nicotine coursing through a typical smoker’s blood. Once hooked, the mice experienced classic signs of nicotine dependence that keep smokers puffing, the research team reports Friday in the journal Science.

“Dependence-related behaviors, including reward, tolerance, and sensitization, occur strongly and at remarkably low nicotine doses” in the mice, the research team wrote.

In humans, reward arrives as a pleasant little jolt of dopamine, a calming brain chemical unleashed by nicotine. The body’s tolerance for the drug leads to more smoking. Sensitization means not feeling good without a nicotine fix, said Henry Lester, a biology professor at the California Institute of Technology who was among the paper’s 10 authors. In mice, researchers saw reward when mice chose nicotine hits over salt, changed body temperatures as evidence of tolerance and more running around among sensitized mice.

Other researchers praised the study.

The findings “not only provide direct evidence of how nicotine promotes dependence, but also raise fundamental questions about the genetics of addiction,” researchers at the Centre Medical Universitaire, in Geneva, Switzerland, wrote in a companion piece.

Could drugs fight addiction?

If the findings in mice hold true for humans, the work points to a specific target for a new drug to attack, others suggest.

People become dependent on nicotine when it parks in nerve cell receptors designed for the chemical acetylcholine. Once nicotine fills that space, dopamine is released. By knowing the specific parking place where nicotine can exact a high toll, a drug could be fashioned to fill it.

“The power lies in the ability to be so specific. In being so specific, you can treat the cause without the ramifications of the side effects,” said Stephen L.