Dyskinesias and impulse control disorders in Parkinson's disease: From pathogenesis to potential therapeutic approaches

Abstract

Dopaminergic treatment in Parkinson's disease (PD) reduces the severity of motor symptoms of the disease. However, its chronic use is associated with disabling motor and behavioral side effects, among which levodopa-induced dyskinesias (LID) and impulse control disorders (ICD) are the most common. The underlying mechanisms and pathological substrate of these dopaminergic complications are not fully understood. Recently, the refinement of imaging techniques and the study of the genetics and molecular bases of LID and ICD indicate that, although different, they could share some features. In addition, animal models of parkinsonism with LID have provided important knowledge about mechanisms underlying such complications. In contrast, animal models of parkinsonism and abnormal impulsivity, although useful regarding some aspects of human ICD, do not fully resemble the clinical phenotype of ICD in patients with PD, and until now have provided limited information. Studies on animal models of addiction could complement the previous models and provide some insights into the background of these behavioral complications given that ICD are regarded as behavioral addictions. Here we review the most relevant advances in relation to imaging, genetics, biochemistry and pharmacological interventions to treat LID and ICD in patients with PD and in animal models with a view to better understand the overlapping and unique maladaptations to dopaminergic therapy that are associated with LID and ICD.

Keywords: Basal ganglia; Behavioral addiction; Dopaminergic drugs; Genetics; Impulse control disorders; Levodopa-induced dyskinesias; Neurochemistry; Neuroimaging; Parkinson's disease; Pathophysiology; Pharmacology; Risk factors.