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Molecular Switch in Brain May End Smokers' Cravings

MONDAY Nov. 24, 2008 -- Blocking a neuropeptide receptor in the brain may be one way to quickly lessen the desire for a cigarette, a new study suggests.

Hypocretin-1, or Orexin A, a short chain of amino acids found in nerve tissue, appears to initiate a series of closely linked biochemical reactions that makes lab rats crave nicotine, the addictive chemical in tobacco, according to researchers at the Scripps Florida research institute in Jupiter.

If duplicated in humans, the finding could be lead to new smoking-cessation treatments, the researchers said.

"Blocking hypocretin-1 receptors not only decreased the motivation to continue nicotine use in rats, it also abolished the stimulatory effects of nicotine on their brain reward circuitries," study leader Paul Kenny, a scientist at Scripps Florida, explained in a news release issued by the institute. "This suggests that hypocretin-1 may play a major role in driving tobacco use in smokers to want more nicotine. If we can find a way to effectively block this receptor, it could mean a novel way to help break people's addiction to tobacco."

In the study, the researchers blocked the hypocretin-1 receptor with low doses of the selective antagonist SB-334867, a commercially available compound often used in research.

The results of the study were published in an online early edition of Proceedings of the National Academy of Sciences, released this week.

The findings might explain why some human smokers spontaneously quit smoking after suffering brain damage in a small area of their frontal cortex. Hypocretin-1 receptors are found in the insula, a walnut-size part of the frontal lobe of the brain, the researchers said.

Previous Scripps research found that hypocretin-1 receptors also play a central role in regulating relapse in cocaine addicts.

Cigarette smoking accounts for about 440,000 deaths and $160 billion in health-related costs annually in the United States. Only about 10 percent of smokers who attempt to quit manage to remain smoke free after one year, the researchers said.

More information

The American Cancer Society has more about quitting smoking.

Posted: November 2008


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