Document Detail

High-frequency stimulation of the subthalamic nucleus prolongs the increase in striatal dopamine induced by acute l-3,4-dihydroxyphenylalanine in dopaminergic denervated rats.
MedLine Citation:
PMID:  17822436     Owner:  NLM     Status:  MEDLINE    
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.
Emilie Lacombe; Carole Carcenac; Sabrina Boulet; Claude Feuerstein; Anne Bertrand; Annie Poupard; Marc Savasta
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-06
Journal Detail:
Title:  The European journal of neuroscience     Volume:  26     ISSN:  0953-816X     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-09-20     Completed Date:  2007-11-20     Revised Date:  2010-09-14    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  France    
Other Details:
Languages:  eng     Pagination:  1670-80     Citation Subset:  IM    
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.
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MeSH Terms
3,4-Dihydroxyphenylacetic Acid / metabolism
Data Interpretation, Statistical
Dihydroxyphenylalanine / pharmacology*
Dopamine / metabolism*
Dopamine Agents / pharmacology*
Electric Stimulation
Extracellular Space / drug effects,  metabolism
Homovanillic Acid / metabolism
Neostriatum / drug effects*,  metabolism*,  physiology
Rats, Sprague-Dawley
Subthalamic Nucleus / physiology*
Synaptic Transmission / drug effects,  physiology
Reg. No./Substance:
0/Dopamine Agents; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 1199-18-4/Oxidopamine; 306-08-1/Homovanillic Acid; 63-84-3/Dihydroxyphenylalanine

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