SUBTHALAMOTOMY IN PARKINSONIAN MONKEYS - BEHAVIORAL AND BIOCHEMICAL-ANALYSIS

Nineteen Macaca fascicularis monkeys were divided into four different groups: Group A (n = 3), control; Group B (n = 3), monkeys treated wit h 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Group C (n = 8) , animals treated with MPTP in which the subthalamic nucleus (STN) was unilaterally lesioned by kainic acid injection; in Group D (n = 5), t he STN was lesioned prior to MPTP administration. Subthalamotomy resul ted in a bilateral improvement of tremor spontaneous activity, bradyki nesia (evaluated by a manual motor test) and freezing in Group C. All these monkeys developed hemichorea contralateral to the lesion. The im provement was maintained and the hemichorea continued until death. The monkeys in group D showed severe hemiballism which persisted througho ut MPTP administration and developed parkinsonian signs mainly on the side ipsilateral to the lesion. Analysis of the in situ hybridization of the mRNA coding for glutamic acid decarboxylase (GAD) of MPTP monke ys showed a significant increase in the mean density of silver grains over every labelled neuron in the globus pallidum lateralis (56.8% ove r control) as well as the globus pallidus medialis (GPM) (45.7% over c ontrol) and the substantia nigra reticulata (SNR) (35.8% over control) . No significant change was observed in the thalamic nucleus reticular 's. Subthalamotomy (Groups C and D) produced a significant reduction i n mRNA GAD expression on the side of the lesion in the GPM and the SNR (34% and 42.3%, respectively) with respect to the ipsilateral (non-le sioned) side and also when compared with parkinsonian monkeys. These r esults confirm and expand, at the cellular level, the paramount role o f STN hyperactivity in the pathophysiology of parkinsonism. The therap eutic consequences of these findings for surgical treatment of Parkins on's disease are discussed.