Nicotine study opens path for anti-smoking drug

(delihayat)

Scientists have pinpointed a source of nicotine craving in the brain, opening up a new path towards drug treatments to help smokers kick their habit, according to a study released Sunday.

Tobacco kills more than five million people every year and accounts for nearly one-in-10 adult deaths, 90 percent of them due to lung cancer.

In experiments with mice and rats, the researchers mapped the functioning of a gene called CHRNA5 that has been previously fingered in nicotine addiction.

The gene controls a receptor - an entry point on the surface of brain cells - which responds to nicotine molecules.

With a normal version of this gene, anything more than a tiny dose of nicotine triggers a message to the brain which says, in effect, "stop consuming," the scientists found.

Larger doses unleash a sense of repulsion, similar to "bad-tasting food or drink," lead researcher Paul Kenny at the Scripps Research Institute in Florida said in an email exchange.

But the effect was quite different in mice in which a tiny sub-unit of the receptor, known as alpha5, had been knocked out.

The negative message was never sent - and as a result, the rodents couldn't get enough of the potent drug.

A similar scenario occurs naturally in some humans, the researchers believe.

Genome-wide screening studies have identified genetic alterations which impair the alpha5 unit's functioning.

Between 30 and 35 percent of the population in the United States is thought to have a form of the CHRNA5 gene that encourages unbridled nicotine craving.

"Our data probably explain the fact that individuals with this genetic variation have increased vulnerability to developing tobacco addiction," Kenny said.

"They are likely to be far less sensitive to the averse properties of the drug, and are thus more likely to acquire a nicotine habit."

On the strength of the new findings, published online in the journal Nature, Kenny has received funding from the National Institute of Drug Abuse to design a new category of drugs.

"This study has important implications for new approaches to tobacco cessation," said Jon Lindstrom, a neuroscientist at the University of Pennsylvania who has investigated other nicotine receptors in the brain and will participate in the follow-up research.

A truly effective anti-smoking drug may require targeting more than one receptor, he said.

"Nicotine influences complex brain circuits involved in reward" - mainly through the release of dopamine - "and memory," Lindstrom explained.

"It has beneficial effects on anxiety and attention, among other things, thus making quitting very difficult. Withdrawal symptoms from quitting smoking make this worse."

Nicotine treatments, such as "patches", boost these reward circuits but can themselves be addictive.

Another widely-used drug reduces the craving and pleasure associated with cigarettes by partially blocking these other receptors.

"Restoring or increasing the aversion to high doses of nicotine may complement these approaches and increase their efficacy, or replace them," Lindstrom said.

mh/ri/rl