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Nicotine Receptors: Role in Nicotine Addiction

Institution: California Institute of Technology
Investigator(s): Ryan Drenan, Ph.D.
Award Cycle: 2006 (Cycle 15) Grant #: 15FT-0030 Award: $20,748
Subject Area: Nicotine Dependence
Award Type: Postdoctoral Fellowship Awards
Abstracts

Initial Award Abstract
Cigarette smoking leads to serious health problems for the smoker, and the treatment of smoking-related illnesses is a tremendous healthcare burden in developed countries. The most effective way to reduce the negative medical and economic impact of smoking is to reduce the number of people who smoke. Unfortunately, people who smoke are not easily able to quit because they are addicted to cigarettes. As it relates to smoking, “addiction” implies that the smoker continues to smoke even though they are aware of the medical risks associated with smoking. It is likely that the reader of this abstract knows a family member or a friend who would like to quit smoking but has found it difficult to do so.

In recent years, as biomedical research has advanced, is has become very apparent that the behavior associated with addiction is the result of cellular and molecular changes in the brain of the addicted person. In every case, the abused drug or addictive substance has a direct effect on specific areas of the brain, often on specific molecules. In addiction to cigarette smoking, the abused drug or substance is called nicotine. When a person inhales cigarette smoke, nicotine from the smoke enters the person’s body through the lungs and makes its way quickly through the bloodstream to the brain. Once in the brain, nicotine causes addiction by attaching to specific molecules known as “ion channels” that are found on the surface of nerve cells. These ion channels are called “nicotinic receptors”, and the attachment of nicotine to them induces a feeling of pleasure or well-being for the smoker.

It is our hypothesis that if a drug were developed that blocked the ability of nicotine to attach to nicotinic receptors, this drug might help people quit smoking because it would stop the feeling of pleasure and well-being that nicotine causes. If the person no longer “felt good” when they smoked, specifically if they no longer had the desire or “craving” to smoke, they would be more likely to quit smoking. We are interested in one particular type of nicotinic receptor, the “alpha 6” receptor. We want to build a new kind of tool to study the receptor to see if “alpha 6” is a good target for drugs that block nicotine. This new tool is a genetically modified mouse that will only activate “alpha 6” when nicotine is delivered to it. We think that, if this tool is made, that it will allow us to learn whether “alpha 6” is a good target to develop a drug against. If it is a good target, we would try to make a drug that blocked “alpha 6”. Hopefully, this drug would help more people quit smoking.