Study reveals link between decision-making disorders and Parkinson's medication

Parkinson's disease (PD), also known simply as Parkinson's, is a nervous system disorder that affects millions of people worldwide. The nerve cell damage associated with Parkinson's can cause tremors, slowed movements, balance problems, and many other symptoms that gradually worsen over time. Although there is no cure, medications are available to treat the symptoms of Parkinson's. However, some of these medications have as yet unexplained side effects – including impaired decision-making ability that leads to potentially harmful behaviors such as pathological gambling, binge eating, and compulsive buying.

In a study published online on August 14, 2024, International Journal of Molecular SciencesResearchers at Fujita Health University in Japan, led by Assistant Professor Hisayoshi Kubota of the Department of Behavioral Neuropharmacology at the International Center for Brain Science (ICBS) at Fujita Health University, have investigated the mechanism by which a drug called pramipexole, or PPX, impairs the decision-making process in mice with Parkinson's disease. The research was co-authored by Professor Taku Nagai of the Department of Behavioral Neuropharmacology at the International Center for Brain Science (ICBS) and Professor Hirohisa Watanabe of the Department of Neurology at the School of Medicine, both at Fujita Health University.

To examine the results of this study in more detail, we must first understand how PPX relieves the symptoms of Parkinson's disease. Parkinson's disease primarily results from the loss of nerve cells, or neurons, that produce a compound called dopamine. Some neurons rely on dopamine for their normal function – they have structures called “dopamine receptors,” which can be thought of as locks that can then be activated using dopamine as a “key.” Drugs like PPX may mimic the function of dopamine and bind to these receptors instead, particularly in patients with Parkinson's who lack dopamine-producing neurons.

To study the effects of PPX on PD, researchers injected mice with a toxin called 6-hydroxydopamine (or 6-OHDA). 6-OHDA damages neurons in a very similar way to what has been observed in the brains of patients with PD. The mice were treated with PPX and then subjected to a touchscreen-based “gambling task” to test their decision-making ability. Interestingly, these mice chose the high-risk, high-reward option much more often—they chose an adverse outcome that involved receiving a large reward (a strawberry milkshake), which also comes with an increased risk of major punishment from exposure to flashing lights.

But which part of the brain is responsible for this behavior? When they examined the brains of mice treated with PPX, they found that a region deep in the brain called the external globus pallidus (GPe) was hyperactivated, or had much higher neuron activity. The researchers then chemically inhibited the neurons in the GPe, which actually reduced the mice's adverse risk-taking. This proved that the hyperactivation of the GPe was indeed responsible for the poor decision-making of the PPX-treated mice.

This study has enormous implications for the treatment of patients with Parkinson's disease.”Our findings may lead to the development of new drugs or interventions specifically targeting the external globus pallidus.explains Dr. Kubota.This would help prevent or reduce decision-making impairments in Parkinson's patients..'

These findings will not only help doctors develop better treatments for Parkinson's disease, but can also help raise awareness among affected patients, their families and the public. Dr. Kubota explains: “Studying the impact of Parkinson's medications on decision-making will help the public better understand the complexity of the disease and its treatment..” He also says “This benefits patients, their families and caregivers and motivates them to think about early treatment and prevention strategies..”

These findings shed new light on the complex brain processes that support our everyday decision-making abilities and hold promise for improving the quality of life of Parkinson's patients. Perhaps we can also learn some important lessons from this study and think twice before making poor decisions in our daily lives!