Parkinson's disease is usually treated with drugs that enhance the brain's dopamine-signaling system. While dopamine helps regulate movement and balance, it also plays a central role in the body's 'reward' system and can reinforce various behaviors -- not all of them productive.

This is the latest in a series of case studies linking such drugs -- called dopamine agonists -- to pathological gambling in Parkinson's patients.

"This lends continued support towards the hypothesis that family of medicines may cause difficulty with behavioral issues in this population of patients," said Dr. M. Leann Dodd, lead author of the study and senior associate consultant in the department of psychiatry and psychology at the Mayo Clinic, in Rochester, Minn.

"It's a very rare side effect but we certainly want anyone treated to understand that the potential is there so that they are open to talk with their neurologists and get on top of these behaviors before they would cause them any damage personally or professionally," she added.

In addition, six of the patients in the new report developed other behavioral problems in tandem with the pathological gambling. These included compulsive eating, increased alcohol consumption, and an obsession with sex.

Obsession with Sex

The study, which appeared online Monday and will be published in the September issue of Archives of Neurology, raises some tantalizing questions about how addictions work and how they might be treated or cured.

Parkinson's disease is characterized by the death of neurons in an area of the brain known as the substantia nigra, and is usually treated with drugs that enhance the dopamine-signaling system. While dopamine, a brain chemical, helps regulate movement and balance, it also plays a central role in the body's "reward" system and can reinforce various behaviors, not all of them productive.

The 11 case studies presented in the new study were startling, not just for the dramatic onset of a dangerous compulsion, but because the reduction or discontinuation of the drug resulted in an equally dramatic cessation of the habit.

One 52-year-old married man started gambling "uncontrollably" after raising the dose of his dopamine agonist. His wife phoned the neurologist to report that her husband had lost more than $100,000, was eating compulsively -- he gained 50 pounds -- and had an obsession with sex that resulted in him carrying on an extramarital affair. The man lost his excessive interest in gambling and sex when the medication was tapered off, according to the report.

Another man with no history of gambling started frequenting casinos for days at a time, exhibited an increased sex drive, drank more alcohol and ate excessively. When his medications were stopped, he reverted to having sex once weekly instead of four times a day.

And one 68-year-old man lost more than $200,000 gambling in six months and left town for days at a time without telling anyone where he was.

Dopamine Stimulation

All of the patients -- who were seen and evaluated between 2002 and 2004 at the Mayo movement disorders clinic -- started gambling only after starting on a dopamine agonist: either pramipexole (nine of the 11 cases) or ropinirole (two cases). The gambling stopped when the drug was reduced or discontinued in eight of the 11 cases. The other three cases were not available for follow-up, the researchers said.

"The fact that they were able to reduce the behavior by reducing or getting rid of the drug implies that it was the drug," said Paul Sanberg, distinguished professor of neurosurgery and director of the University of South Florida Center for Aging and Brain Repair. "It pretty well verifies that dopamine stimulation underlies these negative behaviors."

All the patients were given other therapy or a reduced dose of the same therapy for their Parkinson's symptoms.

Since the paper was submitted for publication, the authors have identified 11 more patients with similar problems. Previous studies have estimated that about 5 percent of people taking pramipexole may have the gambling side effect. Neurologists are beginning to take note and talk to patients about this potential side effect, Dodd said.

Clues into the Nature of Addictive Behavior

The fact that compulsive gambling occurs more frequently with pramipexole may provide clues into the nature of addictive behavior, the researchers said.

Dopamine, a neurotransmitter, can sit on one of several different receptor sites in the brain. Pramipexole, it turns out, has a much higher affinity for the receptor site D3 than others, Dodd said.

"The D3 receptor seems to be localized and more concentrated in the limbic areas of the brain, those areas of the brain that are tied to emotions and internal reward systems," Dodd explained. "It would be very interesting to see whether or not medications that have the opposite effect on D3 might curb some of these behaviors."

Sanberg added: "Does this lead to potential treatments for blocking D3? That's clearly something to look at."

But the dopamine agonists still have value for Parkinson's patients, Dodd said.

"This is not a medication to throw away. It's a good medication. It's often used at lower doses for restless leg syndrome with very good response and we still use it to treat many, many Parkinson's patients," she said. "[The gambling] is reversible. We want patients to be aware so that they can bring it up. If someone were to notice just a slight change of behavior in their loved one, they could mention it to their neurologist."

More information: Visit the National Institute of Neurological Disorders and Stroke for more on Parkinson's disease.