A new discovery has shown why some people cannot give up tobacco and may lead to new anti-smoking treatments. The researchers have found a brain pathway which when defective leads to an uncontrollable desire to smoke. This is a “sub-unit” of a receptor protein sensitive to nicotine.
It is known that this 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 addicted to tobacco.
The study was published in an early online edition of the journal Nature. According to lead researcher Dr Christie Fowler, from the Scripps Research Institute in Jupiter, Florida, US, “If the pathway isn’t functioning properly, you simply take more. Our data may explain recent human data showing that individuals with genetic variation in the alpha5 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 team 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). These nAChRs are made up of different types of subunits, one of which is the alpha5 subunit authors write. When the team “knocked out” this subunit in mutant mice and rats, the animals were much more determined to seek out higher doses of nicotine. Animals with unaltered alpha5 subunits showed more restraint.
“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.”
Now in the next steps the team joined with colleagues from the University of Pennsylvania to develop drugs that reduce nicotine addiction by boosting alpha5 subunit signalling. 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.
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