From Our 2008 Archives

Gene Linked to Early Nicotine Addiction

Researchers Say Genetics May Help Explain Positive Reactions to First Cigarette

By Salynn Boyles
WebMD Health News

Reviewed By Louise Chang, MD

Aug. 8, 2008 — If you're a smoker or former smoker, you probably remember your first cigarette and whether it brought on fits of coughing or a pleasant buzz.

Now new research suggests a link between that initial reaction to smoking and a specific gene variant that has also been linked to a greater likelihood for becoming addicted to nicotine.

And a separate study published this week also sheds new light on why some people seemingly get hooked when they light their first cigarette.

The two studies join a growing body of research exploring individual differences in vulnerability to nicotine addiction.

"The cigarette companies have told us for years that smoking is an individual choice," longtime nicotine researcher Ovide Pomerleau, PhD, of the University of Michigan tells WebMD. "But it is increasingly clear that for some people that isn't really the case."

Nicotine Addiction and Genes

In their study published online today in the journal Addiction, Pomerleau and colleagues report on the association between initial smoking experiences, current smoking patterns, and a specific variant in a nicotine receptor gene known as CHRNA5.

The study included 435 smokers and nonsmokers. All the nonsmokers had smoked at least one cigarette during their lives (and no more than 100), but had never become hooked. The regular smokers had smoked at least five cigarettes a day for the past five years or longer.

Smokers in the study were eight times more likely than nonsmokers to report that their first cigarettes gave them a pleasurable buzz.

The smokers were also much more likely to have the variant of the CHRNA5 gene that has been linked with increased susceptibility to nicotine addiction.

"It really is a triple whammy," Pomerleau says. "People with this genetic makeup find smoking pleasurable from that first cigarette and they are more likely to get addicted and develop lung cancer."

Nicotine and the Brain

In another study that examined the same question in a different way, researchers from the University of Western Ontario identified key areas within the brain that appear to regulate sensitivity to nicotine's rewarding effects.

"Nicotine doesn't give you the euphoric high that drugs like morphine give," researcher Steven R. Laviolette, PhD, tells WebMD. "In fact, during initial exposure many people get sick. But while we understand quite a bit about how the brain processes the rewarding effects of nicotine after dependence is established, we know very little about this initial vulnerability."

The researchers targeted a brain pathway that has been linked to drug dependence.

In a series of experiments in rats, they identified and were able to manipulate two "hotspots" that controlled whether the rats were rewarded or repelled by their initial exposure to nicotine.

The findings were reported this week in the August issue of the Journal of Neuroscience.

"If humans have naturally occurring differences in the dopamine system in this area of the brain, that might be one reason why some people would find their initial exposure to cigarettes rewarding and others would get sick," Laviolette says.

Both researchers say their findings could have implications for the discovery of new, targeted therapies that are much more effective than current treatments for smoking cessation.

Pomerleau says such treatment could be a reality within a few years.

"Things are moving really fast in this field," he says. "We are making new discoveries all the time."

SOURCES: Sherva, R. Addiction, Aug. 8, 2008, online edition. Laviolette, S. Journal of Neuroscience, Aug. 6, 2008, online edition. Ovide Pomerleau, PhD, professor of psychology and psychiatry, University of Michigan, Ann Arbor. Steven Laviolette, PhD, department of anatomy and cell biology, Schulich School of Medicine and Dentistry, University of Western Ontario.

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