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Gene clue to nicotine addiction

5 November 2004
By BioNews
Appeared in BioNews 283

The identification of a single brain protein that controls nicotine addiction could pave the way for new drugs to help people give up smoking, US researchers say. Scientists at the California Institute of Technology bred mice with an altered version of a single gene, which makes the animals hypersensitive to the effects of nicotine. The study, published in the journal Science, shows that brain proteins called acetylcholine receptors  are crucial to the process of nicotine addiction.

Addiction is thought to occur when nicotine or other drugs 'hijack' the brain's reward system, which is normally triggered by activities such as eating or sex. The chemical dopamine is then released in the brain, which leads to feelings of contentment. Nicotine triggers dopamine production by sticking to acetylcholine receptor proteins in the brain, which are made up of several different subunits. Previous research has shown mice lacking the genes for one of these subunits are less susceptible to becoming addicted to nicotine.

In the latest study, the researchers bred mice in which they 'tweaked' the gene that makes another one of the subunits, called alpha4. They found that a single change in this gene made the mice much more sensitive to the effects of nicotine - they became hooked at levels 50 times lower than that found in the blood of a typical human smoker. Study author Henry Lester said the work showed that the alpha4 receptor unit 'is not only necessary for nicotine addiction, but is sufficient for nicotine addiction'. The research also supports the idea that naturally occurring genetic variations could be responsible for an inherited predisposition to addiction in some people.

The mice displayed 'dependence-related' behaviours, such as choosing nicotine over food or water. The researchers think that it may be possible to treat nicotine addiction in humans, by finding a way to stop the drug from sticking to the acetylcholine receptors. Robert West, of University College London, said the study could help develop medicines that 'target the receptors involved in nicotine dependence but not others', which would minimise side effects. He told BBC News Online that the drug company Pfizer are currently testing a new drug called varenicline, which targets this receptor.

SOURCES & REFERENCES
Clue to nicotine addiction found
BBC News Online |  5 November 2005
Hope for the hooked after scientists find nicotine gene
The Independent |  5 November 2004
Mutant Mice Help Shed Light on Tobacco Addiction
Reuters |  4 November 2004
What genes tell us about nicotine addiction
Science |  5 November 2004
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