Motivational Deficits in Parkinson’s Disease: Role of the Dopaminergic System and Deep-Brain Stimulation of the Subthalamic Nucleus

Beyond motor symptoms, Parkinson’s disease (PD) patients also exhibit a cluster of neuropsychiatric symptoms, which are now recognized as major contributors to morbidity, severely impairing the patient’s quality of life. Among them, apathy, with a frequency that varies from 16.5 to 70 % depending on the assessment scale used and the population studied, appears to be a major neuropsychiatric feature of PD. In addition, apathy is viewed as a major postoperative complication of deep brain stimulation of the subthalamic nucleus (STN-DBS). Despite this prevalence, the pathogenesis of apathy in PD remains elusive. Importantly, levodopa and dopaminergic agonists, such as the D2/D3 receptor agonist ropinirole, greatly attenuate apathy in Parkinsonian patient, suggesting an important role of dopamine in its pathophysiology. Nevertheless, it is difficult to disentangle the specific role of the dopaminergic denervation and that of DBS in the development of apathy since it has been reported that STN-DBS influences dopaminergic function on its own. Approaches relying on experimental models of PD and STN-DBS thereby can be useful tools to dissect the potential causal contribution of these two factors and their possible interactions. In this chapter, we present recent experimental and clinical data, which provides a better understanding of the role of the dopaminergic system and STN-DBS in the motivational deficits observed in PD. In light of this literature, apathy can be considered as a plurifactorial motivational deficit with a critical role of dopamine acting synergistically with the DBS of STN regions associated with the nigrostriatal and the mesolimbic system.