February 16, 2007
The dopamine levels around Row 37 were unquestionably low.
After a 4 1/2-hour delay on an icy Kennedy Airport runway, and a flight in which the economy-class food ran out even before takeoff, Stephen Dewey could sense the misery all around him in the back of American Airlines Flight 59.
How fitting that the San Francisco news conference he was missing yesterday afternoon would be focused on the myriad pathways in the brain that involve a neurotransmitter linked to good moods, reward, movement and pleasure — none of which were in abundance on his flight.
Despite the trying day, the senior scientist at Brookhaven National Laboratory and his colleagues should have plenty to discuss at this morning’s lab-sponsored symposium on dopamine-mediated drug addiction at the annual convention of the American Association for the Advancement of Science in San Francisco.
Armed with sophisticated imaging techniques that have “advanced our knowledge of substance abuse by leaps and bounds,” Dewey and other scientists are mapping out addiction pathways that may open up wide avenues of treatment options. So far, most roads are running through the versatile dopamine, which can mitigate the foul moods of long-delayed airline passengers but also is a central player in drug addiction studies.
Surging dopamine levels, in fact, are a hallmark of drug abuse: the rapid spike brings the euphoria that fuels the addiction. Without that quick-fire mood alteration, Dewey says, repeated drug use wouldn't seem all that rewarding. Dose for dose, he says, no known drug elevates dopamine levels higher than the exceedingly addictive drug methamphetamine, or meth. Researchers have measured a dopamine increase of as much as 5,000 percent after meth use, compared with a relatively modest 80 percent spike from nicotine.
All this information may be pointing toward some new addiction solutions. Dewey said a chemical in the brain known as GABA, for example, shuts down dopamine release in the same way that a main fuse box can turn off all the lights.
Through research with animals and study of volunteers, he helped discover that a drug called vigabatrin can increase GABA levels and thus keep dopamine from surging in response to drug use. Initially designed as an anti-epileptic drug, vigabatrin in low doses has yielded a surprisingly high 40 percent success rate in treating a group of Mexican patients for heroin addiction — enough to encourage a start-up drug company to pursue expanded clinical trials in the United States.
“We are optimistic, enthused and openly engaged,” said Patrick McEnany, chief executive of Coral Gables, Fla.-based Catalyst Pharmaceutical Partners.
In a phone interview, McEnany said he expects to begin enrolling patients by the end of June for a vigabatrin clinical trial aimed at cocaine addicts, with a similar trial for meth abusers starting three months later.
Other pathways also are coming into focus. Nora Volkow, director of the National Institute on Drug Abuse, has found that stimulants lose some of their ability to elevate dopamine levels when taken by either cocaine abusers or alcoholics. Imaging studies also suggest similar dopamine-regulated pathways are engaged whether someone is actively craving cocaine or a cheeseburger.
Research led by Joanna Fowler, director of the Center for Translational Neuroimaging at BNL, has pointed toward another intriguing pathway traveled by an enzyme called monoamine oxidase. Fowler said she and her colleagues discovered that the enzyme, which helps to break down dopamine and other mood-influencing neurotransmitters, is dramatically reduced in the brains of smokers — the effects of a tobacco smoke component.
With more mood-boosting dopamine as a result, she said, the research suggests depressed smokers may be self-medicating by taking in compounds that simulate the effects of anti-depressants. Following that notion, other scientists believe an enzyme blocker that helps keep dopamine levels steady might be a useful tool for helping people quit smoking.
Dopamine stabilizers might have been useful on the flight taken by Fowler and Dewey. After staying up all night Wednesday to finish his presentation, Dewey at least avoided some of the misery as he slept peacefully through the entire ground delay.
Copyright 2007 Newsday Inc.