In a new study, researchers have identified a region of the brain linked to impaired decision-making skills seen in patients receiving Parkinson’s disease treatment.
Nerve cell damage associated with Parkinson’s can cause tremors, slowed movements, problems with balance, and many other symptoms which worsen gradually over time.
Although there is no cure, there are medications available that can treat symptoms. Some of these medications, however, have previously unexplained side effects – including impaired decision-making that leads to potentially harmful behaviours such as pathological gambling, binge eating and compulsive shopping.
In a new study, researchers have now investigated the mechanism by which a drug called pramipexole or PPX impairs the decision-making process in mice with Parkinson’s disease.
How PPX works to alleviate Parkinson’s symptoms
Parkinson’s mainly results from a loss of nerve cells or neurons that produce a compound called dopamine. Some neurons are dependent on dopamine for their regular functioning – they have structures called ‘dopamine receptors’ which can be thought of as locks which can then be activated using dopamine as the ‘key’.
Drugs like PPX can imitate the function of dopamine and bind to these receptors instead, especially in patients with Parkinson’s who lack dopamine-producing neurons.
To study the effects of PPX on Parkinson’s, the researchers injected the brains of mice with a toxin called 6-hydroxydopamine (or 6-OHDA). 6-OHDA damages neurons in a very similar manner to that observed in the brains of patients with Parkinson’s.
The mice were treated with PPX and then subjected to a touchscreen-based ‘gambling task’ to test their decision-making skills. Interestingly, these mice picked the high-risk/high-reward option much more often – they opted for a disadvantageous outcome where they received a large reward (of strawberry milkshake), which also comes with an increased risk of a large punishment by exposure to flashing lights.
But which part of the brain is responsible for this behaviour?
Investigating the brains of mice treated with PPX revealed that a region deep inside the brain called the external globus pallidus (GPe) was hyperactivated, or showed a much higher level of neuron activity. The researchers then chemically inhibited the neurons in the GPe, which actually reduced disadvantageous risk-taking activity in the mice.
This proved that hyperactivation of the GPe was indeed responsible for poor decision-making in the mice treated with PPX.
This study has huge implications for treating patients with Parkinson’s disease.
“Our findings could lead to the development of new medications or interventions that specifically target the external globus pallidus,” explains study lead Assistant Professor Hisayoshi Kubota from the Division of Behavioral Neuropharmacology, International Center for Brain Science (ICBS), Fujita Health University.
‘This would help to prevent or reduce decision-making impairments in Parkinson’s disease patients.’
Besides helping medical professionals develop better treatments for Parkinson’s disease, these findings can also help improve awareness among affected patients, their families, as well as the general public.
Dr. Kubota explains that: “Investigating how Parkinson’s disease medications affect decision-making will help the public to better understand the complexity of the disease and its treatment.
“This will benefit patients, their families and carers, and motivate them to consider early care and preventive strategies.”
These findings shed new light on the complex processes in the brain that aid our everyday decision-making skills, and promise to improve quality of life for patients affected by Parkinson’s disease. Maybe we can take away some important lessons from this study as well, and think twice before we indulge in poor decision-making in our daily lives!
The study has been published in the International Journal of Molecular Sciences, and was carried out by researchers at Fujita Health University in Japan.
The research was co-authored by Professor Taku Nagai from the Division of Behavioral Neuropharmacology, International Center for Brain Science (ICBS), and Professor Hirohisa Watanabe from the Department of Neurology, School of Medicine, both at Fujita Health University.
