Pathophysiology

The establishment of a model of parkinsonism through the administration of MPTP to nonhuman primates has provided important insights into new therapeutic strategies. A typical parkinsonian syndrome develops in the animals that is characterized by dopaminergic-cell loss in the substantia nigra and striking abnormalities in the spontaneous activity and sensorimotor responses of neurons in the basal ganglia.⁹⁴,⁹⁵ A fundamental discovery has been that the dopamine-deficiency state is associated with increased activity of the inhibitory γ-aminobutyric acid (GABA)–employing (GABAergic) output nuclei in the basal ganglia, the internal segment of the globus pallidus, and the pars reticulata of the substantia . . .