Parkinson's disease is associated with degeneration of the dopamine (DA)- containing neurons of the nigrostriatal bundle (NSB). However, the neurological symptoms that accompany this disease do not emerge until the degenerative process is almost complete. This phenomenon can be observed in a rat animal model of the disorder that is produced by the intracerebral administration of the selective neurotoxin 6-hydroxydopamine (6-HDA). Studies utilizing this model suggest that the capacity to withstand NSB injury is a consequence of increased synthesis and release of DA from those NSB neurons that remain together with a decrease in the rate at which that DA is inactivated. The experiments proposed in this application are designed to examine several aspects of this hypothesis, including the mechanism by which the hyperactivity might occur. Also to be examined are several aspects of the basic neurobiology of monoaminergic systems, including the interactions among neurotransmitters within striatum and the role of extracellular DA in these interactions. Findings from these studies may have important implications for the treatment of a, variety of neurological and psychiatric diseases, as well as our understanding of neuroplasticity in monoaminergic systems.
