High-frequency stimulation of the subthalamic nucleus prolongs the increase in striatal dopamine induced by acute l-34-dihydroxyphenylalanine in dopaminergic denervated rats

摘要

High-frequency stimulation of the subthalamic nucleus (STN-HFS) is a powerful approach for treating the motor symptoms of Parkinson’s disease. It results in clinical improvement in PD patients, further reducing L-3, 4-dihydroxyphenylalanine (L-DOPA) requirement and thus L-DOPA-induced dyskinesia. However, it remains unclear how STN-HFS modifies the response to L-DOPA. We investigated the effect of STN-HFS on striatal extracellular concentrations of dopamine and its metabolites following acute L-DOPA administration in intact or partially dopaminergic denervated (DA PL) rats. L-DOPA treatment significantly increased striatal dopamine levels in intact and DA PL animals, with the maximal effect observed 1 h after L-DOPA injection. This increase was more pronounced in DA PL rats (ipsilateral to the lesion) than in intact animals. It remained fairly stable 1 h after the maximal effect of L-DOPA and then decreased towards basal values. STN-HFS in intact rats had no effect on the maximal L-DOPA-induced increase in striatal extracellular dopamine concentration or the return to basal values, the profiles observed being similar to those for non-stimulated intact animals. Conversely, STN-HFS amplified the L-DOPA-induced increase in striatal dopamine levels during the stimulation period (1 h) in DA PL rats, and this increase was sustained throughout the post-stimulation period (2.5 h), without the return to basal levels observed in stimulated intact and non-stimulated rats. These new neurochemical data suggest that STN-HFS interferes with L-DOPA effects, probably synergically, by stabilising dopamine levels in the striatum, and shed light on the mechanisms of STN-HFS in PD.