In the Dyskinetic Rat During Chronic L-DOPA Treatments for Parkinson’s Disease
Parkinson’s disease (PD) is a chronic neurodegenerative disorder with a profound hypokinetic phenotype that is characterized by the preferential loss of dopaminergic neurons stemming from the substantia nigra pars compacta and innervating the dorsal striatum. Oxidative stress is thought to contribute to Parkinsonian symptoms, and several lines of evidence suggest that the standard treatment strategy of dopaminergic replacement therapy via administration of L-DOPA may serve to increase oxidative stress and potentiate cell death. We are correlating striatal H2O2 and DA dynamics with behavioral changes that result from chronic L-DOPA administration in a rodent model of PD over several weeks. Specifically, H2O2 is increased during periods of intense rotation, and DA concentrations decrease with the onset of rotation. These studies will aid in our understanding of how oxidative stress modulates nigrostriatal DA signaling, and will demonstrate how these signals correspond with the development of dyskinetic movements in the treatment of PD.