The one-two punch
If you want to increase the level of a chemical inside the body, you could make more of the chemical. Or you could interfere with the body's mechanism for destroying it.

Recent information concerning dopamine, a neurotransmitter associated with pleasure and well-being, indicates that cigarette smoke might use both techniques for raising dopamine levels. If true, it could have serious consequences for smoking cessation programs.

Nicotine has long been known to stimulate the release of dopamine. Now, research by scientists at Brookhaven National Laboratory (BNL) in New York points toward -- but does not prove -- another mechanism for cigarette addiction. They've found something in cigarette smoke that seems to be slowing the breakdown of dopamine.

These brain slices show levels of the "killjoy" enzyme MAO B in the brains of two people. The non-smoker at the top has plenty of MAO B, but the smoker at bottom has much less -- a sign that something in cigarette smoke is destroying MAO B, allowing the pleasure chemical dopamine to tell the body it likes smoking and wants to continue. The Brookhaven researchers believe it's not just nicotine that is sustaining the addiction, but another agent as well. These scans were made with positron emission tomography, which captures the signal from a short-lived radioactive tracer to make color images of brain activity. Courtesy Brookhaven National Lab Center for Imaging and Neurosciences.

The researchers tracked MAO B, an enzyme that breaks down dopamine in the brain. In general, after they are released and transmit their signal, excess dopamine and other neurotransmitters are broken down, or are taken back up and stored in the neuron. If they remain free, they send spurious signals.

FYI, MAO B = ?

If cigarettes are indeed slowing the breakdown of dopamine, it could add up to a one-two punch, says chemist Joanna Fowler of BNL. "Nicotine is known to elevate brain dopamine. But the markedly lower MAO B in the smokers' brains suggests that whatever is inhibiting MAO B could actually be acting in concert with nicotine to enhance dopamine's activity."

The research is preliminary, and it's not clear that the 40 percent reduction in MAO B actually does increase dopamine levels, Fowler stresses. "It's not a real leap that it could enhance dopamine, but we don't know if this really translates into an enhancement in the smoker's body."

Who dun it?
One of the key unknowns is which chemical, among the 4,000 or so identified in cigarette smoke, might be causing the reaction. Fowler says it's not nicotine, based on earlier studies that showed nicotine did not influence MAO B. The difficulty of finding the suspect is not just due to the sheer number of compounds in smoke. If the chemical binds irreversibly to a receptor on brain cells, "it could be something present in minuscule quantities that builds up over years of smoking." Something like that would be extremely difficult to isolate, she says.

The Brookhaven project arose by serendipity (that's scientese for "good luck"), Fowler says, while the research group was studying aging. When neurons (defined) shrink, there's an expansion of glial cells (defined). Since glial cells contain a lot of MAO B , the researchers decided to make images of MAO B levels as a way to track them.

Curiously, they noticed that some subjects had 40 percent less MAO B than others. On investigation, it turned out that what distinguished the low-MAO B group was a history of smoking.

If smokers indeed have an elevated level of brain dopamine, it could have implications for smoking cessation, Fowler speculates. With more dopamine, they might be happier, more content, and bound to their habit by a mechanism that involves the MAO B inhibitor substance as well as nicotine. So just as cigarette quitters sometimes receive nicotine replacement therapy, "it may make sense to give MAO B inhibitors" to lessen the shock of drug withdrawal, Fowler says.

Any practical impact of these discoveries is in the future, but the backdrop for this work is the creation of legions of new smokers. Every day, thousands of young people start to smoke.
What's new, scientifically speaking, about kids, butts and ads?

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