Brain scientists try to manage dopamine’s effects

WASHINGTON -- The good, the bad and the ugly: That's a quick summary of the effects of dopamine, a natural brain chemical that is linked to pleasure, addiction and disease.

This little molecule -- it consists of only 22 atoms -- is essential to life but can be a curse sometimes. Too much or too little of it can lead to drug abuse, reckless thrill-seeking, obesity, the tremors of Parkinson's disease, even restless-leg syndrome.

Although dopamine was identified almost a century ago, brain scientists are still trying to figure out how to manage its undesirable effects, such as cocaine or nicotine addiction.

"There is no currently approved medication for treating cocaine addiction," Nora Volkow, the director of the National Institute on Drug Abuse, said recently as she announced the successful preliminary test of a possible future vaccine for the dangerous drug.

"We are looking at the potential for new medications that reduce the brain's sensitivity to these conditioned drug cues and would give patients a fighting chance to manage their urges," Anna Childress, a psychiatrist at the University of Pennsylvania School of Medicine in Philadelphia, told a conference of neuroscientists in Washington. "We have a brain hard-wired to appreciate rewards, and cocaine and other drugs of abuse latch onto this system."

Dopamine is the key to that system. A "neurotransmitter" that helps brain cells, or neurons, communicate with one another, dopamine is released into the brain by pleasurable experiences such as eating, having sex or indulging in drugs.

Its presence creates feelings of satisfaction, enjoyment or excitement, and so it motivates people to repeat behavior, good or bad. Dr. Jay Giedd, a psychiatrist at the National Institute of Mental Health in Rockville, Md., explained dopamine's effects in a radio interview this year:

"If we make good decisions, our dopamine goes up. It tells our brain, you know, 'Good call, that was the right move, you know, do that again next time,' and it literally changes the anatomy of the brain. It strengthens certain connections. It decreases others."

The problem is that behavior that shouldn't be repeated also releases dopamine.

Researchers are studying dopamine's role in conditions such as the following:

• Addiction: Drugs such as cocaine, amphetamines and nicotine flood nerve circuits in the brain with dopamine. This produces the euphoric effects that smokers and drug users crave and motivates them to repeat the behavior.

• Obesity: Recent studies have found a connection between obesity and low dopamine levels in the brain.

Experiments with rats show that a weakened dopamine system reduced the pleasurable feeling associated with eating. The rats compensated by overeating and soon became obese, according to Emmanuel Pothos, a neuroscientist at Tufts University School of Medicine in Boston. He said there was evidence that obese humans also had a shortage of dopamine.

"We eat not only for nourishment but also for pleasure," wrote Gerald Weissmann, the editor in chief of The FASEB Journal, an experimental biology publication. "Now we know why so many people stay addicted to food: It fuels the midbrain pleasure machinery."

• Gambling: Prescription medications that stimulate dopamine production can have a strange side effect, occasionally turning people into reckless gamblers.

"Some ordinary people with regular lives taking this medication all at once started to gamble and engage in hazardous games of luck, a behavior that stopped after discontinuing the drug," Birgit Abler, a researcher at the University of Ulm, Germany, told the neuroscientist conference. Dopamine also plays a role in other serious ailments. Scientists hope to discover ways to ease their effects.

• Parkinson's disease: The slow-developing movement disorder is caused by the gradual deaths of neurons that supply dopamine, according to James Surmeier, a Parkinson's expert at Northwestern University. Patients suffer uncontrollable trembling and stiffness of the limbs.

Researchers are seeking drugs that slow down the loss of dopamine neurons, said Marina Picciotto, a neuroscientist at Yale University.

The herbal supplement L-Dopa, also known as Levodopa, may be taken to create more dopamine, thereby relieving the shortage that leads to Parkinson's.

• ADHD: A brain-imaging study at Brookhaven National Laboratory in Upton, N.Y., found low levels of dopamine in people with attention deficit hyperactivity disorder.

"These deficits in the brain's reward system may help explain the clinical symptoms of ADHD, including inattention and reduced motivation, as well as the propensity for complications such as drug abuse and obesity among ADHD patients," the National Institute on Drug Abuse's Volkow reported in the Sept. 9 issue of the Journal of the American Medical Association.