Several studies have shown that antagonists of
N-methyl-D-aspartate receptors provide protection of the dopaminergic nigrostriatal pathway in animal models of
Parkinson's disease. Since the substantia nigra compacta receives a moderate glutamatergic innervation from the subthalamic nucleus, we tried to determine whether subthalamic nucleus lesion could prevent the toxicity of the selective dopaminergic
neurotoxin 6-hydroxydopamine (6-OHDA). Experiments were carried out on four groups of rats. Group 1 (n = 10) received a unilateral injection of
6-hydroxydopamine in the striatum and group 2 (n = 10) received
kainic acid in the subthalamic nucleus. Group 3 (n = 10) received an injection of
kainic acid in the subthalamic nucleus and 1 week later an injection of
6-OHDA in the striatum. Group 4 (n = 5) received the same treatment but
kainic acid was replaced by saline.
Apomorphine induced an ipsilateral rotation in rats of groups 2 and 3 and a contralateral rotation in rats of groups 1 and 4. The number of
tyrosine hydroxylase-immunoreactive cells in the pars compacta of the substantia nigra was not significantly decreased on the side ipsilateral to
6-OHDA striatal injection in rats of groups 1 and 4. These results show that subthalamic nucleus lesion provides neuroprotection of the dopaminergic nigrostriatal pathway against
6-OHDA toxicity and opens a new way for slowing or stopping the progression of
Parkinson's disease.