Modeling the Presymptomatic Stage of Hemi-Parkinsonian State in Animals (Rodents and Monkeys)

The behavioral and functional states preceding the onset of specific parkinsonian symptoms were studied at an early (presymptomatic) stage of hemi-parkinsonian syndrome development in rodents and monkeys. The consecutive steps of neuropathological traits development—cognitive impairments developing from weeks 1–2 of rotenone exposure, minor motor impairments on weeks 3–4 before the development of pronounced motor dysfunction, and some biochemical indicators—were studied using the model of hemi-parkinsonian syndrome in rodents induced by chronic administration of low doses of rotenone toxin. The characteristics of visually guided saccades (VGS) while an instrumental conditioning task performing were studied using the model of hemi-parkinsonian syndrome in nonhuman primates (Macaca mulatta) chronically treated with low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxin. As MPTP syndrome progresses, an increase in the latencies of VGS and a decline in their accuracy with the retention of an instrumental conditioning performance have been shown. The negative behavioral effects in rodents and primates and biochemical effects in rodents manifested at the presymptomatic stage of the disease, suggest to consider them as early markers of a hemi-parkinsonian syndrome.