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managed for the U.S. Department of Energy
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Released: February 21, 1996
Contact: Mona S. Rowe, 631 344-5056
Why Do People Smoke?
Research at Brookhaven Lab Looks Beyond Nicotine
Upton, NY -- Nicotine may not be the only tobacco smoke ingredient that hooks smokers into addiction, suggests research at the U.S. Department of Energy's Brookhaven National Laboratory.
In the first report of a distinct biochemical effect triggered in the brain by cigarette smoke, Brookhaven scientists have found that smokers have a greatly reduced level of a crucial brain enzyme. Since previous studies elsewhere have acquitted nicotine as the culprit, something else in cigarette smoke is at work in inhibiting the enzyme.
As reported in the February 22 issue of Nature, smokers had an average of 40 percent less of the enzyme MAO B than nonsmokers and those who had kicked the habit. This finding, drawn from brain scans of 20 subjects, may also help explain smokers' paradoxically lower risk of developing Parkinson's disease, and the higher incidence of smoking among drug addicts and those with psychiatric disorders. For those who smoke but want to quit, MAO B could one day be the target of specialized treatments.
MAO B is short for monoamine oxidase B. Previous studies have shown that it breaks down dopamine, a neurotransmitter associated with movement, motivation and reward. Less MAO B could result in enhanced dopamine activity, rewarding and reinforcing the behavior that caused the increase in dopamine, behavior such as smoking.
In the study, the brain-imaging technique known as positron emission tomography (PET) was used to scan the brains of eight smokers, eight nonsmokers and four former smokers. The subjects, all volunteers, were healthy men and women between the ages of 23 and 86.
Before scanning, each subject was given a trace amount of a substance that is known to bind to MAO B, but had been specially "labeled" with short-lived radioactivity. In PET scanning, such as substance is known as a radiotracer. For the MAO B study, the radiotracer used was a version of the commonly used anti-Parkinson's drug L-deprenyl, specially prepared by BNL chemists.
The radiotracer, which gives off subatomic particles known as positrons when it decays, allows scientists to track the movement of the tracer in the subjects' brains, and hence the location and concentration of MAO B in various brain regions.
The radioactively labeled L-deprenyl delivers only a small dose of radiation to the subject because of its very short half-life (20 minutes). All PET studies at BNL are reviewed by the Laboratory's independent Human Subjects Research Committee.
"Nicotine is known to elevate brain dopamine," said BNL chemist Joanna Fowler. "But the markedly lower MAO B levels in the smokers' brains suggest that whatever is inhibiting MAO B could actually be acting in concert with nicotine to enhance dopamine's activity by preventing its breakdown."
"Increased dopamine, and the accompanying feeling of pleasure, would then reinforce smokers' smoking behavior and continue their addiction," said Fowler's colleague, psychiatrist Nora Volkow. "This effect could also reinforce other addictions and also act in a therapeutic fashion in individuals with psychiatric disorders like depression."
Lower MAO B levels in smokers' brains could also help explain why smokers have a lower incidence of Parkinson's disease than non-smokers. Explained Fowler, "When MAO B breaks down dopamine, it produces hydrogen peroxide as a byproduct. Hydrogen peroxide is a source of free radicals, which could cause damage to nerve cells." Parkinson's disease is a chronic, progressive nerve disease aggravated by a shortage of dopamine.
Said Fowler, "Even though smoking is responsible for thousands of deaths and illnesses each year, we know relatively little about how smoking affects the human brain. But if we want to find ways to help people fight their addiction to tobacco and quit smoking, we need to develop a better understanding of why people smoke."