Parkinson's Foundation

Parkinson's Foundation is using its 2021 distribution to fund:

  • Circuit Mechanisms of Impulse Control Disorder in Parkinsonism
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    PROJECT TITLE: Circuit Mechanisms of Impulse Control Disorder in Parkinsonism

    Investigators/Authors: Xiaowen Zhuang (Mentor: Alexandra Nelson), The Regents of the University of California, San Francisco

    Objective: Chronic treatment of Parkinson’s Disease (PD) with dopaminergic medications is commonly associated with behavioral side effects, often termed impulse control disorder (ICD). A better understanding of how ICD develops would inform prevention and treatment strategies for ICD in PD.

    Background: Approximately 17% of all medicated PD patients suffer from ICD. ICD behaviors include compulsive gambling, shopping and sexual behaviors, usually requiring the patient to greatly reduce or stop dopamine agonist therapy at the cost of alleviating motor symptoms. So far, there is no effective treatment of ICD. Despite the high prevalence rates of ICD in medicated PD patients, and the challenges of treating it, we have very limited knowledge of why it develops in PD patients.

    Methods/Design: This study aims to determine how dopamine agonist interacts with one vulnerable brain region, the striatum, to increase the risk of ICD. The striatum is thought to be important in decision-making and action selection. To model ICD, we have developed a mouse behavioral assay, built on the delay discounting task, which has been used to measure impulsivity in PD patients. Delay discounting is a cognitive phenomenon found in healthy individuals, in which the value of a reward decreases according to the time needed to wait for it. In ICD, delay discounting will be abnormal. We will also monitor the activity of brain cells in parkinsonian mice during the delay discounting task before and after dopamine agonist treatment, and compare the responses seen in one main cell type within the striatum. We believe that the activity of one main group of cells will be important in learning key aspects of delay discounting, and this learning will be profoundly disrupted in parkinsonian mice in response to dopamine agonist.

    Relevance to Diagnosis/Treatment of Parkinson’s disease: We believe these studies will shed light on underlying mechanism of impulse control disorder in PD patients and provide new information needed to improve dopamine replacement therapy with a goal of reducing impulse control disorder.