Acute and chronic administration of 1-methyl-4-phenylpyridinium

This chapter introduces two models of Parkinson's disease (PD), and discuses their utility in the examination of impaired energy metabolism on DA homeostasis and for pharmacological testing of potential neuroprotective compounds. One of models presented is created by a chronic, continuous low dose administration of MPP+ into the cerebral ventricle. The other model results from a single acute administration of MPP+ or malonate into the striatum. The choice of which model to use depends on the research question. The chronic MPP+ model is progressive in nature, presents with neuropathology seen in PD brain, exhibits low inter-animal variability, no mortality, and because of the unilateral lesion, the animals are essentially healthy. While the model requires further characterization, it nonetheless has demonstrated its utility for pharmacological testing of neuroprotective agents. Moreover, because of the progressive nature of degeneration in the model, it can be used for testing therapeutic approaches targeted at the many cellular processes involved in degeneration. The single acute MPP+ or malonate PD model has proven to be especially beneficial when coupled with other injection formats or microdialysis to examine dynamic changes in brain regions subjected to a metabolic stress.