Читать книгу Current Concepts in Movement Disorder Management - Группа авторов - Страница 31

Animal models of dopamine depletion, in which dopaminergic toxins such as 6-hydroxy-dopamine or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are used to produce permanent loss of dopamine neurons have helped us to delineate the steps that link dopamine loss to the clinical manifestations of parkinsonism. Early studies in MPTP-treated primates emphasized the importance of global changes in activity along the direct and indirect pathways. Studies of electrical and metabolic activity changes in the basal ganglia of MPTP-treated primates showed a reduction of neuronal firing in GPe, and increased activity in STN, GPi, and SNr (discussed in ref. [4]). These data led to the development of the “rate model” of PD, postulating that striatal dopamine depletion leads to increased firing rates in the inhibitory striatal output neurons of the indirect pathway, resulting in the inhibition of GPe, and subsequent disinhibition of STN and GPi/SNr. Possibly, the loss of dopaminergic facilitation of the direct inhibitory pathway further increases the GPi/SNr activity. Increased basal ganglia output from GPi/SNr to the thalamus was considered to be responsible for excessively inhibiting thalamocortical interactions, and, thus, reducing excitability of cortical neurons.