Brain Pathway Inhibits Motivation to Quit Smoking
Quitting smoking is one of the best things you can do for your health, but as any smoker knows, this can be easier said than done. Scientists learned last year that nicotine binds to a certain receptor in the brain that contributes to nicotine addiction. More recently, researchers from The Scripps Research Institute in Florida have learned of another brain pathway that increases vulnerability to tobacco addiction.
Faulty Brain Receptor Increases Vulnerability to Nicotine
Lead study author and associate professor Paul Kenny examined the effects of a specific receptor in the brain known as nicotinic acetylcholine receptor subunit a5(a5* nAChRs), located in a discrete pathway called the habenulo-interpeduncular tract.
The team used genetically altered mice who were lacking a5* nAChRs in their study. When given access to high doses of nicotine, the “knockout” mice consumed much larger quantities than normal mice.
The team then used a virus that “rescued” the expression of a5* nAChRs in the medial habenula, which plays a role in the control of emotional and social behaviors, and other areas of the brain into which it projects. The nicotine consumption patterns of the knockout mice returned to a normal range, suggesting that a drug targeting this mechanism could be developed as an anti-smoking therapy.
“It was unexpected that the habenula, and brain structures into which it projects, play such a profound role in controlling the desire to consume nicotine,” said Christie Fowler, first author of the study and research associate in the Kenny laboratory. “The habenula appears to be activated by nicotine when consumption of the drug has reached an adverse level. But 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 α5 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,” she concludes.
Tobacco smoking is one of the leading causes of death worldwide, with more than five million people dying each year as a result, according to statistics cited in the study. Scientists have established that a tendency towards smoking can be inherited – more than 60 percent of the risk of becoming addicted to nicotine can be attributed to genetic factors.
“We believe that these new data establish a new framework for understanding the motivational drives in nicotine consumption and also the brain pathways that regulate vulnerability to tobacco addiction,” said Kenny.
“Habenular α5* Nicotinic Receptor Signaling Regulates Nicotine Intake,” published online January 30, 2011 in an advance issue of the journal Nature.