Parkinson's disease is associated with degeneration of the nigrostriatal bundle. However, the neurological symptoms that accompany this disease do not emerge until the degenerative process is almost complete. Early studies with animals models suggested that the extensive preclinical phase of Parkinsonism was due in part to the development of a compensatory hyperactivity within remaining dopamine-containing neurons. Other studies suggested that systemic administration of L-DOPA could reduce the neurological symptoms once they emerged by further increasing the availability of dopamine in striatum. Subsequent work has supported both hypothesis.