Biomedicine

Gambling and Parkinson's Disease

Scientists are searching for clues into why some Parkinson’s drugs trigger compulsive behavior.

Headache, nausea, dry mouth … and risk of gambling? It’s undoubtedly an odd side effect, but in the past year, it’s become clear that people taking drugs for Parkinson’s disease have a greater risk of developing compulsive disorders, such as gambling, hypersexuality, and shopping addiction. Now scientists are trying to better understand the root of the bizarre behavior in order to prevent the problem in Parkinson’s patients and perhaps to better understand the disorder in other people with gambling addictions.

“We see people develop compulsive gambling and sexual behavior with exposure to dopamine drugs,” says Daniel Weintraub, a geriatric psychiatrist at the University of Pennsylvania. “Understanding why may help us understand these problems in non-Parkinson’s patients.”

With Parkinson’s disease, neurons that produce a brain chemical called dopamine are lost, leading to characteristic tremors and a host of other symptoms. Patients are often treated with levodopa, a chemical that replaces lost dopamine in the brain. More recently, physicians have begun treating patients with drugs that stimulate dopamine receptors. It is this latter class, known as dopamine agonists, that is linked to a markedly increased risk of gambling.

Dopamine–a crucial chemical messenger in the brain–plays a central role in the brain’s reward system. Dopamine neurons are active when we do pleasurable things, like eating or having sex, and also play a central role in drug addiction. Recently, studies have shown that compulsive gamblers exhibit different activity patterns in dopamine-rich parts of their brain.

While anecdotal stories of compulsive gambling in Parkinson’s patients have trickled in over the past few years, two studies released last year present solid evidence that patients taking dopamine agonists have an increased risk of compulsive behavior. In one study of almost 300 Parkinson’s patients, 10 became pathological gamblers after starting treatment–nearly double the number expected based on rates observed in the general population. The 10 patients lost an average of $150,000. Others showed signs of hypersexuality and compulsive shopping.

In a new study, designed to help the medical community better understand how dopamine drugs affect behavior, scientists at the Wellcome Trust Center for Neuroimaging, in London, gave healthy people one of two different drugs: one that boosts dopamine levels, and one that blocks dopamine receptors. Participants then played a gambling game in which different symbols were associated with winning or losing different amounts of money. To win, players had to learn which symbols were profitable versus unprofitable.

The researchers found that those who took the dopamine-boosting drug were better at predicting which choice would win more money, according to results to be presented at the American Academy of Neurology meeting in Boston next week. However, when they lost, those with the dopamine boost did not behave any differently than those taking a placebo. “Dopamine teaches you to get what you want but not to avoid what you fear,” says Mathias Pessiglione, a neuroscientist now at the Salpetriere Hospital, in Paris, who led the study. “One can imagine that excessive levels of dompanine could create an imbalance between experiencing reward and experiencing punishment. That could explain the compulsive behavior observed with dopamine replacement therapy.”

In this case, dopamine likely acts by boosting the cellular changes that underlie learning, but only in the positive condition. “Dopamine acts in [the] brain by reinforcing synapses that lead to rewarding behavior,” says Pessiglione.

Further studies that will specifically examine Parkinson’s patients are now under way or in the planning stages.For example, Weintraub intends to use brain-imaging technologies to look specifically at dopamine levels in the brains of Parkinson’s patients with compulsive disorders, both while the patients take their medication and after they stop. Pessiglioneand his collaborators are now running similar tests on people with Parkinson’s disease, as well as Tourette’s syndrome and obsessive-compulsive disorders, both of which have been linked to dopamine dysfunction.

Scientists hope that such studies will explain why some patients are more at risk of developing these behaviors than others are, and that the studies will ultimately help clinicians when prescribing drugs for their patients.

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