Summary: Pramipexole, a Parkinson’s disease ( PD ) drug, impairs decision-making by hyperactivating the brain’s external globus pallidus ( GPe ) region. This analysis uncovers how the treatment, while powerful for PD ailments, can lead to risky activities like gambling.
The findings provide a chance for developing solutions that target the GPe to lessen these side effects. Understanding this process may lead to improved quality of life for Parkinson’s sufferers.
Important Information:
- Pramipexole hyperactivates the GPe, causing weak decision-making in PD.
- After receiving PPX, animals choose hazardous outcomes more frequently, according to research.
- These mental negative results may be reduced by targeting the GPe in PD individuals.
Origin: Fujita Health University
Parkinson’s disease ( PD), also known simply as Parkinson’s, is a disorder of the nervous system that affects millions of people worldwide. The brain cell damage associated with Parkinson’s can cause tremors, slowed activities, issues with balance, and many other signs that increase gradually over time.
Although there is no known cure, there are treatments that can handle PD symptoms. Some of these treatments, however, have previously unknown side effects – including impaired decision-making that leads to potentially damaging activities such as compulsive gambling, binge eating and compulsive shopping.
Now, in a , study published online on 14 August 2024 in the , International Journal of Molecular Sciences, researchers 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, 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 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.
To examine the findings of this study more closely, we must first understand how PPX helps to lessen PD signs. Loss of muscle tissue or cells that produce a substance called serotonin is a major cause of PD.
Some neurons have structures known as “dopamine receptors,” which can be thought of as locks that can then be activated using serotonin as the “key.” Some neurons depend on serotonin for normal functioning.
Medicines like PPX may imitate the dopamine receptors ‘ actions and connect to them otherwise, mainly in PD patients who lack dopamine-producing neurons.
The researchers injected the brains of rabbits with a chemical called 6-hydroxydopamine ( or 6-OHDA ) to investigate the effects of PPX on PD. In a way that is very similar to what is observed in the brains of people with PD, 6-OHDA damage cells.
The animals were treated with PPX and finally subjected to a touchscreen-based’ playing work’ to check their decision-making skills. These mice chose the high-risk/high-reward option much more frequently, which is a disadvantageous outcome because it comes with a higher risk of receiving a significant reward ( a strawberry milkshake ), as well as a higher risk of receiving a significant punishment from flashing lights.
Which area of the brain is in charge of this behaviour, though? A region called the external globus pallidus ( GPe ), which is located deep inside the brain and is the subject of a study on mice treated with PPX, was either hyperactivated or displayed significantly higher levels of neuron activity.
The researchers therefore biologically inhibited the GPe’s cells, which in turn reduced the mice’s risk-taking behavior. This demonstrated that the GPe’s hyperactivation caused the animals treated with PPX to make poor decisions.
This research has great implications for treating people with Parkinson’s disease.
Our findings may lead to the development of novel treatments or therapies that specifically target the outside plexus pallidus, says Dr.  . Kubota. This may help to prevent or minimize decision-making deficits in Parkinson’s disease patients.’
Besides helping medical professionals produce better solutions for Parkinson’s disease, these results can even help increase awareness among affected patients, their families, as well as the common people.
Dr.  , Kubota, explains that” Investigating how Parkinson’s disorder medicines affect decision-making will help the public to better understand the complexity of the disease and its treatment”.
He also says” This will benefit patients, their families and caregivers, and motivate them to consider early maintenance and preventive methods”.
These findings provide new insight into the intricate mental processes that help our daily decision-making abilities and promise to enhance the quality of life for those with Parkinson’s disease.
Maybe we can think twice before making bad decisions in our daily lives and taking away some important teachings from this research as well.
About this Parkinson’s condition and neuropharmacology analysis reports
Author: Hisatsugu Koshimizu
Source: Fujita Health University
Contact: Hisatsugu Koshimizu – Fujita Health University
Image: The image is credited to Neuroscience News
Original Research: Start exposure.
” Pramipexole Hyperactivates the External Globus Pallidus and Impairs Decision-Making in a Rat Model of Parkinson’s Disorder” by Hisayoshi Kubota et cetera. Molecular Sciences International Journal
Abstract
Pramipexole Hyperactivates the External Globus Pallidus and Impairs Decision-Making in a Rat Model of Parkinson’s Condition
In patients with Parkinson’s disease ( PD), dopamine replacement therapy with dopamine D2/D3 receptor agonists induces impairments in decision-making, including pathological gambling. The physiological mechanisms underlying these undesirable effects are still elusive.
Here, in a mouse model of PD, we investigated the effects of the dopamine D3 receptor ( D3R ) -preferring agonist pramipexole ( PPX ) on decision-making.
PD model mice were created by administering the toxin 6-hydroxydopamine bilaterally to the dorsal striatum. Following treatment with PPX increased detrimental options characterized by a high-risk/high-reward in the touchscreen-based Iowa Gambling Task.
Treatment with the careful D3R enemy PG-01037 was able to stop this result. In model mice treated with PPX, the number of c-Fos-positive cells was increased in the external globus pallidus ( GPe ), indicating dysregulation of the indirect pathway in the corticothalamic-basal ganglia circuitry. In compliance, chemogenetic suppression of the GPe restored standard c-Fos activation and saved PPX-induced bad decisions.
These results demonstrate that PD design mice’s decision-making is impacted by the hyperactivation of GPe cells in the direct pathway.
The findings provide a potential mechanism and therapeutic target for compulsive gambling that were observed while receiving D2/D3 sensor pharmacotherapy for PD individuals.
