The purpose of the proposed study is to assess a model of Parkinson's disease in small mammals. Use of small animals such as the rat will permit extensive neurochemical, physiologic and pharmacologic investigation. Rats will be injected with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a drug which produces Parkinsons-like disease in man and monkey. During and following chronic treatment, motor functions which are basic to mammmals, and which are known to be altered in Parkinsonian patients will be assessed. These include motor activity levels, walking patterns, balance and equilibrium reactions, and fluidity of movement. The time course for development of dysfunction and the persistence of deficits even after termination of MPTP injections are important aspects of this study. As dopamine is known to be depleted in Parkinson's disease, neurochemical assays and immunocytochemical procedures will be performed to see if MPTP alters the activity of dopamine neurons in the rat. Finally, electrophysiologic studies of spontaneous activity in single cells of the basal ganglia will be performed to determine the nature of changes in cellular function which accompany altered motor function and nigral cell pathology. If MPTP is effective in producing Parkinsonian-like basal ganglia dysfunction in the rat it would offer the opportunity to follow the progression of changes in basal ganglia structure and function which lead to a defined disease state. The ability to identify the components or sequences of events in the change from normal to abnormal function mmay permit earlier intervention and disruption of disease processes and progressions.
