Researchers have found that by removing a protein from cells located in the brain's reward center blocks the anxiety-reducing and rewarding effects of nicotine.

According to a new animal study in the July 27 issue of Journal of neuroscience, The findings will help researchers understand better how nicotine affects the brain.

Nicotine works by binding to proteins called nicotine receptors on the surface of the brain cells. Nicotine acts as a stimulant and is the main factor responsible for the dependence-forming properties of tobacco smoking. According to the American Heart Association, nicotine addiction has historically been one of the hardest addictions to break.

In the new study, researchers led by Tresa McGranahan, Stephen Heinemann, PhD, and T.K. Booker, PhD, of Salk Institute for Biological Studies, found that removing a specific type of nicotine receptors from the brain cells that produce dopamine, a chemical released in response to reward, makes mice less likely to seek out nicotine. The mice also did not show reductions in anxiety like behaviors normally seen after nicotine treatment. Smokers commonly report anxiety relief as a key factor in continued smoking or relapse.

Studies showed that blocking the alpha4 nicotine receptor in the Ventral Tegmental Area (VTA), a region of the brain important in motivation, emotion, and addiction, decreases the reward properties of nicotine. Nonetheless, it was unclear how nicotine produced pleasurable feelings. To target the brains response to nicotine, researchers developed mice with a mutation that left it unable to produce alpha4 receptor, but only dopamine brain cells. Compared to normal mice, the mice without the Alpha4 receptors in the cells spent less time searching to obtain nicotine. Nicotine also failed to reduce anxiety like behaviors in the mutant mice, as it normally does in healthy mice.

Identification of the type of nicotine receptors necessary for the key features of nicotine addiction reward and anxiety, may help us better understand the pathway that leads to nicotine dependence, and potential treatment for the one billion cigarette smokers worldwide," said McGranahan.

Tobacco related death remains a major killer throughout the world, causing more than 5 million deaths per year.

Published in the july 27 issue of the Journal of Neuroscience.