BNL Addiction Symposium

Abstract Details

February 16, 2007, San Francisco, CA  |  Symposium Home

Monoamine Oxidase in Smoking: Role in Addiction and Health

Author: Joanna Fowler
Director, Center for Translational Neuroimaging,
Brookhaven National Laboratory

Cigarette smoking is a massive yet potentially preventable public health problem worldwide. However, the development of strategies for prevention and treatment require a better understanding of why people smoke and how smoking affects the brain, directly in the relevant clinical population, the cigarette smoker. With the development of brain-imaging technologies and a wide variety of radiotracers, we now have the opportunity to examine the actions of tobacco smoke on the human brain. Such studies allow us to study the pharmacological actions of cigarette smoke and provide important clues to understanding smoking behavior and the epidemiology of smoking (for example, the high rate of smoking in people with psychiatric disorders and addictions to other substances), as well as a basis for understanding an observed decreased risk of Parkinson's disease in smokers. This knowledge will be essential for developing successful prevention and treatment strategies.

Most studies on the effects of tobacco smoke on the brain have focused almost entirely on nicotine, the major addictive component of tobacco smoke. Our brain-imaging studies have focused on the enzyme monoamine oxidase (MAO), an enzyme that breaks down dopamine and other neurotransmitters associated with reward and mood. Our research using positron emission tomography (PET) scanning demonstrates that brain MAO in smokers is reduced by ~ 40% relative to non-smokers and former smokers (Figure 1). Our studies also show that, in addition to a reduction in brain MAO, smokers also have reduced levels of MAO in other organs (Figure 2).

These studies also indicate that MAO inhibition by tobacco smoke is not caused by nicotine but by other substances in the tobacco leaves. Furthermore, MAO inhibition by tobacco smoke requires chronic administration. In addition, it is long lasting. Our imaging studies have shown that smokers who abstain overnight have the same level of MAO inhibition the next day.

Since MAO breaks down neurotransmitters producing hydrogen peroxide as a by-product, MAO inhibition would be associated with enhanced activity of dopamine and other neurotransmitters, and decreased production of hydrogen peroxide. Since hydrogen peroxide is a potential source of damaging free radicals, decreased hydrogen peroxide production may be one of the neurochemical links explaining the reduced rate of Parkinson’s disease in smokers.

Since MAO inhibitor drugs are useful in the treatment of depression, brain MAO inhibition by tobacco smoke may explain why the rate of smoking is so high in individuals with depression and other psychiatric disorders. More specifically, smokers who are depressed may be self-medicating because nicotine (which releases neurotransmitters that improve mood) and MAO inhibition (which reduces the rate of neurotransmitter destruction) simulates the effects of anti-depressant medications. Since the rate of smoking is very high in alcoholics and in individuals addicted to other drugs, it is possible that smoking makes other drugs more reinforcing. This is supported by recent studies showing that MAO-inhibitor drugs enhance the reinforcing effects of nicotine and also are associated with an enhancement of cocaine-induced elevation of brain dopamine in animals.

This body of research on MAO in smokers has already stimulated the search for and discovery of MAO inhibitor compounds in tobacco smoke as well as trials investigating the use of MAO inhibitors for smoking cessation.

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Last Modified: January 31, 2008

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