Objective/Rationale:
Pramipexole (Mirapex®) is a drug that is effective at alleviating movement deficits associated with Parkinson’s disease. However, pramipexole can induce compulsive behaviors and behavioral addictions, such as problem gambling, in some patients. Mirtazapine, an atypical antidepressant reduces the effects of drug addiction in pre-clinical models and in humans. This study aims to determine if mirtazapine can reduce pramipexole-induced gambling-like behavior in a model of PD, while leaving the motor benefits intact.
Project Description:
The PD models will be implanted with small wires into the reward system of the brain, and they will be trained to press a lever to receive a stimulation reward. The models will learn that pressing one lever results in a small reward (low stimulation current) delivered with 100% probability, and another lever will result in a larger reward, but delivered with varying lower probabilities. Choosing the larger reward when its probability is low (for example, 10%) is considered risky, gambling-like behavior. This way we will measure gambling-like behavior following pramipexole administration in models with and without mirtazapine.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Parkinson’s patients that are treated with pramipexole and exhibit compulsive behaviors, such a problem gambling, are often taken off this drug and cannot benefit from its therapeutic effects. This study may show that concurrent treatment with mirtazapine in these patients can allow them to benefit from movement enhancing effects of pramipexole without the compulsive behavioral side effects.
Anticipated Outcome:
We predict that pramipexole will improve motor deficits in the models and also increase gambling-like behavior. We also predict that mirtazapine will reduce gambling-like behaviors but not the motor improvements. These experiments may enhance our understanding of how pramipexole acts to increase compulsive behaviors in some Parkinson’s patients, and may lead to more effective treatments for this side effect.