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Some of the most common treatments for Parkinson's disease have side effects that impair sensible decision making. A study has now identified a part of the brain where these side effects might be triggered, potentially giving us a way to manage them.
Led by researchers from Fujita Health University in Japan, the study looked at the effects of pramipexole on mice. Pramipexole can be used on its own or with other medications to manage Parkinson's symptoms, but it can also cause harmful compulsive behaviors like gambling, eating, or shopping to excess.
Pramipexole works by mimicking the neurotransmitter dopamine, which is reduced in the brains of people with Parkinson's disease. Here, the researchers engineered mice to show neuron damage similar to that caused by Parkinson's before treating them with pramipexole.
The mice were then set on risk and reward tasks designed to stand in for gambling, and sure enough, the mice showed compulsive behavior – choosing high risk and high reward options that match how addicted gamblers might act.
Close observation of the mouse brains led the researchers to a part of the nervous system called the external globus pallidus, which helps regulate voluntary and subconscious movements and was abnormally active in the gambling mice.
The external globus pallidus has actually already been successfully targeted to manage Parkinson's through deep brain stimulation, and this research suggests it could also help in managing the side effects of pramipexole too.
"Our findings could lead to the development of new medications or interventions that specifically target the external globus pallidus," says Hisayoshi Kubota, a neuroscientist from Fujita Health University.
"This would help to prevent or reduce decision-making impairments in Parkinson's disease patients."
When the mice were injected with drugs to 'turn off' the external globus pallidus, the behavior of the animals became more normal in the gambling task, providing further evidence that the region's neurons and their connections aren't functioning as they should.
It's still early days for this research, but knowing where in the brain the wiring is going awry – assuming it's the same in humans as it is in mice – is a good start. It might even help those without Parkinson's who have compulsive habits, the researchers suggest, once further studies have been carried out.
While a means of reversing the disorder's neurodegeneration is yet to be discovered, improvements in therapies that slow its progress can make a significant difference. These new findings should help make those treatments more effective.
"Investigating how Parkinson's disease medications affect decision-making will help the public to better understand the complexity of the disease and its treatment," says Kubota.
"This will benefit patients, their families and carers, and motivate them to consider early care and preventive strategies."
The research has been published in the International Journal of Molecular Sciences.
