Study reveals impairments in decision-making linked to Parkinson’s drug

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

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

To take a closer look at the findings of this study, we first need to understand how PPX works to relieve PD symptoms. PD is mainly due to loss of nerve cells or neurons that produce a compound called dopamine. Some neurons depend on dopamine for their normal function – they have structures called ‘dopamine receptors’ which can be thought of as locks which can then be activated using dopamine as a ‘key’. Drugs like PPX can mimic the function of dopamine and bind to these receptors, especially in PD patients who lack dopamine-producing neurons.

To study the effects of PPX on PD, the researchers injected the brains of mice with a toxin called 6-hydroxydopamine (or 6-OHDA). 6-OHDA destroys neurons in a very similar way to that seen in the brains of PD patients. Mice were treated with PPX and then given a touchscreen-based “gamble task” to test their decision-making skills. Interestingly, these mice chose the high-risk/high-reward option much more often – choosing an aversive outcome where they received a large reward (strawberry milkshake), which also comes with an increased risk of large punishment from exposure to flashing lights.

But which part of the brain is responsible for this behavior? Examination of the brains of mice treated with PPX revealed that a region deep within the brain called the globus externus (GPe) was hyperactivated, or showed a much higher level of neuronal activity. The researchers then chemically inhibited neurons in the GPe, which actually reduced aversive risk-taking activity in the mice. This proved that GPe overactivation was indeed responsible for poor decision-making in the PPX-treated mice.

This study has huge implications for the treatment of patients with Parkinson’s disease. “Our findings could lead to the development of new drugs or interventions that specifically target the external globus pallidus,” explains Dr. Kubota.This would help prevent or reduce impairments in decision-making in patients with Parkinson’s disease.’

In addition to helping medical professionals develop better treatments for Parkinson’s disease, these findings may also help improve awareness among affected patients, their families, and the general public. Dr. Kubota, explains that “Investigating how Parkinson’s drugs affect decision-making will help the public better understand the complexity of the disease and its treatment.” It also says “This will benefit patients, their families and carers and motivate them to consider early care and prevention strategies.”

These findings shed new light on the complex processes in the brain that aid our everyday decision-making skills and promise to improve the quality of life of patients suffering from Parkinson’s disease. Perhaps we can take away some important lessons from this study and think twice before indulging in poor decision making in our daily lives!