Hope for the hooked after scientists find nicotine gene

A single gene could be responsible for determining how easily people become addicted to smoking, according to a report published today.

By tweaking a gene in the brains of mice, US researchers were able to create a hypersensitive breed that becomes hooked at a nicotine level 50 times lower than that found in a typical smoker's blood.Once addicted, the mice show the classic signs of nicotine dependence.

Scientists believe the discovery could offer ways to help smokers unable to give up. By producing a drug that somehow targets the neurons in the brain with the nicotine sensitivity, scientists could help reduce the four million smoking-related deaths each year.

The results, reported in the journal Science, showed that people's ability to give up smoking - which, as Mark Twain quipped, can be done "hundreds of times" - depends strongly on the chemical structure of a particular neuron in the brain called the alpha-4 nicotinic acetylcholine receptors.

Receptors are like chemical locks in the brain which react to particular molecular keys. In humans, nicotine generates a "reward" feeling by producing a jolt of dopamine, a calming chemical, when it is taken up by the appropriate brain receptors.

Addiction occurs when the nicotine "parks" in the receptors, which are intended for a different chemical transmitter, acetylcholine. But continued exposure to nicotine means the receptors become less sensitive, which leads to the smoker's need for a regular "fix".

Henry Lester, a biology professor at the California Institute of Technology, where the work was done, said that the mice showed classic signs of being addicted - including choosing nicotine before a food such as salt, and frenetic activity.

"Dependence-related behaviours, including reward, tolerance, and sensitisation, occur strongly and at remarkably low nicotine doses" in the mice, the research team wrote.

Stephen Dewey, a scientist at Brookhaven National Laboratory, who has studied epilepsy drugs to treat nicotine addiction, said: "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."

But Daniel McGehee, a neurobiologist at the University of Chicago who specialises in nicotine receptors, warned that interfering with nicotine's effect on the brain might also dull such experiences as eating food or drinking water.

"That [receptor] pathway is not there to promote tobacco use. It's there to promote healthy behaviours that lead to the survival of our species," Dr McGehee said. Tampering with it "may interfere with our ability to find pleasure and joy in normal, healthy things."

Professor Lester said: "What we have done is to show that a particular molecule is not only necessary for nicotine addiction, but is sufficient for nicotine addiction. When the particular alpha receptor is activated by nicotine - and no other receptors - that is sufficient to produce some of the effects associated with addiction."

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