Subthalamic nucleus lesion in rats prevents dopaminergic nigral neuron degeneration after striatal 6-OHDA injection: behavioural and immunohistochemical studies.

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.