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Brain defect stimulates compulsive desire to smoke

A discovery that explains why some people cannot give up tobacco may lead to new anti-smoking treatments.

Scientists have identified a brain pathway which when defective leads to an uncontrollable desire to smoke.

It involves a component, or "subunit", of a receptor protein sensitive to nicotine.

Normally, the pathway dampens down the urge to consume more nicotine when levels of the drug reach a critical level.

But in some people the mechanism is faulty, causing them to become hooked on tobacco.

Lead researcher Dr Christie Fowler, from the Scripps Research Institute in Jupiter, Florida, US, said: "If the pathway isn't functioning properly, you simply take more.

"Our data may explain recent human data showing that individuals with a genetic variation in the alpha 5 nicotinic receptor subunit are far more vulnerable to the addictive properties of nicotine, and far more likely to develop smoking-associated diseases such as lung cancer and chronic obstructive pulmonary disease."

The scientists, whose work is reported in an early online edition of the journal 'Nature', carried out tests on animals with a genetic mutation that leaves them without the receptor subunit.

They found that the animals consumed far more nicotine than normal.

Nicotine, the major addictive component of tobacco smoke, acts in the brain by stimulating proteins called nicotinic acetylcholine receptors (nAChRs).

The nAChRs are made up of different types of subunits, one of which is the alpha 5 subunit.

When the subunit was "knocked out" in mice and rats, the animals were much more determined to seek out higher doses of nicotine.

The scientists have now joined forces with the University of Pennsylvania to develop drugs that reduce nicotine addiction.

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