High-frequency stimulation of the subthalamic nucleus prolongs the increase in striatal dopamine induced by acute l-3,4-dihydroxyphenylalanine in dopaminergic denervated rats.
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.
Lacombe
Emilie
E
Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Equipe Dynamique des Réseaux Neuronaux du Mouvement, Grenoble, France.
Carcenac
Carole
C
Boulet
Sabrina
S
Feuerstein
Claude
C
Bertrand
Anne
A
Poupard
Annie
A
Savasta
Marc
M
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003627:Data Interpretation, Statistical; D003714:Denervation; D004295:Dihydroxyphenylalanine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D020531:Subthalamic Nucleus / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology