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Do Dopamine Agonists Spark Gambling Compulsion?

If dopamine agonists can trigger pathological gambling, then they may do so by supercharging dopamine receptors in an area of the brain known to give rise to craving and pleasure.

Forty-one-year-old "Derrick" and 63-year-old "George" had two things in common: both had Parkinson's disease and both, within one to two months after starting to take a dopamine-agonist medication, felt a strong urge to gamble.

George had gambled at casinos about four times a year, and he had never overspent his self-allotted gambling limit. Now, he said, he felt an "incredible compulsion" to gamble two or three times a week, even when he "logically knew it was time to quit."

As for Derrick, he had never gambled before, but began gambling on the Internet and lost $5,000 within a few months.

The cases of Derrick and George were reported July 11 on the Web site of Archives of Neurology, along with those of nine other individuals who also had Parkinson's disease and had started to show signs of pathological gambling after taking a dopamine agonist. The report came from a group of psychiatrists and neurologists at the Mayo Clinic. The lead author was M. Leann Dodd, M.D., a psychiatrist and senior associate consultant in Mayo's Department of Psychiatry and Psychology.

Dodd and her group also conducted a MEDLINE search for any mention of Parkinson's patients engaging in pathological gambling after getting a dopamine agonist. They found 17, they stated in their report.

Twenty-eight cases hardly constitute compelling evidence that there is a connection between dopamine agonists and pathological gambling. Moreover, most Parkinson's patients who take dopamine agonists do not experience the desire to gamble excessively, Dodd told Psychiatric News. In fact, she said, she has never heard of any other medication having been linked with pathological gambling.

Hypotheses Offered

Nonetheless, she and her colleagues suspect that dopamine agonists triggered the pathological gambling in the cases they reported and hypothesized why this may have occurred.

For example, they were able to follow up eight of the 11 individuals they cited, and once these individuals tapered or stopped taking a dopamine agonist, their urge to engage in pathological gambling ceased as well.

Also, after taking dopamine agonists, six of the patients felt a strong desire not just to gamble but also to engage to excess in other behaviors such as eating, drinking alcohol, having sex, and making purchases. And once these patients stopped taking the drug or took less, their urges in all of these domains declined dramatically. One of these patients was George. He stopped taking his dopamine agonist abruptly. Two days later, he felt his longings to engage in such behaviors rapidly resolve. It was "like a light switch being turned off," he said.

Authorities Weigh Evidence

Two pathological gambling authorities—Suck Won Kim, M.D., a professor of psychiatry at the University of Minnesota, and Jon Grant, M.D., an associate professor of psychiatry there—told Psychiatric News that they have little doubt that dopamine agonists can trigger an impulse to gamble. Indeed, Grant said, "Those of us who treat pathological gamblers have also seen many movement-disordered patients who report pathological gambling onset secondary to starting dopamine agonists."

And the reason why dopamine agonists might trigger pathological gambling, Kim explained, is that they exert their pharmacological actions not only in the basal ganglia that govern Parkinson's symptoms, but in the nucleus accumbens. The nucleus accumbens is known to give rise to craving and pleasure, which in turn are mediated by dopamine. Thus, if a dopamine agonist overly excites dopamine receptors in the nucleus accumbens, it might well "trigger cravings to gamble and excitement when winning," Kim speculated.

Specific Version of Receptors May Matter

But if dopamine agonists can truly ignite the urge to gamble, then why do they awaken it in only a few patients who take them? Dodd suspects that the answer may lie in which genetic version of dopamine receptors one has inherited.

In other words, one version of the receptors might be more receptive to dopamine stimulation than another. In fact, Dodd said, she and her colleagues may be "doing a genetic study looking for possible polymorphisms in the gene that codes for the dopamine D₃ receptors that may be contributing to the way this small population of patients is responding to the dopamine agonists."

Grant believes that in addition to genetic research, functional brain imaging could help answer an even more intriguing question: Why did the patients who only gambled secondary to taking dopamine agonists not also develop problems with sex, alcohol, or eating?

"Pathological Gambling Caused by Drugs Used to Treat Parkinson Disease" can be accessed at <http://archneur.amaassn.org> by searching on the study title.

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