High-frequency stimulation of the subthalamic nucleus prolongs the increase in striatal dopamine induced by acute l-3,4-dihydroxyphenylalanine in dopaminergic denervated rats.

Emilie Lacombe 1 Carole Carcenac 1 Sabrina Boulet 1 Claude Feuerstein 1, 2 Anne Bertrand 1 Annie Poupard 1 Marc Savasta 1, 2, *
* Auteur correspondant
1 GIN - Grenoble Institut des Neurosciences
2 CHU Grenoble
Abstract : High-frequency stimulation of the subthalamic nucleus (STN-HFS) is a powerful approach for treating the motor symptoms of Parkinson's disease (PD). It results in clinical improvement in patients with PD, further reducing the 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 stabilizing dopamine levels in the striatum and shed light on the mechanisms of STN-HFS in PD.
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European Journal of Neuroscience, Wiley, 2007, 26 (6), pp.1670-80. 〈10.1111/j.1460-9568.2007.05747.x〉
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Emilie Lacombe, Carole Carcenac, Sabrina Boulet, Claude Feuerstein, Anne Bertrand, et al.. High-frequency stimulation of the subthalamic nucleus prolongs the increase in striatal dopamine induced by acute l-3,4-dihydroxyphenylalanine in dopaminergic denervated rats.. European Journal of Neuroscience, Wiley, 2007, 26 (6), pp.1670-80. 〈10.1111/j.1460-9568.2007.05747.x〉. 〈inserm-00391584〉

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