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Scripps Research scientists reveal key mechanism governing nicotine addiction
Date:1/30/2011

ay 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."

A Previously Unknown Pathway Inhibits Motivation

Tobacco smoking is one of the leading causes of death worldwide, with more than five million people dying each year as a result of it, according to statistics cited in the study. Smoking is considered the cause of more than 90 percent of lung cancer deaths. 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 laid at the door of genetic factors.

Nicotine is the major addictive component of tobacco smoke, and nicotine 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 α5 subunitthe focus of the new study.

In their experiments, the Scripps Research scientists set out to determine the role of nAChRs-containing α5 subunits (α5* nAChRs) in regulating nicotine consumption.

First, the team assessed the addictive properties of nicotine in genetically altered mice lacking α5* nAChRs. The results showed that when these "knockout" mice were given access to high doses of nicotine, they consumed much larger quantities than normal mice. Next, to determine if the subunit was responsible for the sudden shift in appetite for nicotine, the scientists used a virus that "rescued" the expression of α5* nAChRs only in the medial habenula and areas of the brain into which it projects. The results showed the nicotine consumption patterns of the knockout mice returned to a normal range. <
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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