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MODIFICATIONS NEUROCHIMIQUES INDUITES PAR LA STIMULATION HAUTE FREQUENCE DU NOYAU SOUS-THALAMIQUE AU SEIN DES RESEAUX NEURONAUX IMPLIQUES DANS LES CIRCUITS MOTEURS ET LEURS INTERACTIONS AVEC UN TRAITEMENT A LA L-DOPA

Etude par microdialyse intracérébrale chez le rat sain et hémiparkinsonien.

Abstract : High frequency stimulation (HFS) of the subthalamic nucleus (STN) counteracts the motor symptoms of Parkinson's disease (PD), but also diminishes dramatically the L-Dopa-induced dyskinesia (LID) following an important, or even total reduction of L-Dopa doses in stimulated patients. However, the precise mechanisms underlying the therapeutic effectiveness of deep brain stimulation are not elucidated yet. In particular, the possible interactions existing between the effects of both STN HFS and L-Dopa remain to be elucidated.
Our work was carried out in the anesthetized animal, intact or hemiparkinsonian, acutely or chronically treated with L-Dopa, and submitted or not to HFS depending on the experiments. In a first set of experiments, we analyzed in intact rats STN HFS-induced neurochemical modifications (variations of glutamate and GABA contents measured by brain microdialysis) occuring in structures away from STN but implicated in motor networks, such as Fr3 cortex, thalamic ventromedial nucleus and superior colliculus. In a second set of experiments, we tried to determine if STN HFS could modulate the response to a chronic or an acute L-Dopa treatment on the contents of dopamine or its metabolites (DOPAC and HVA), glutamate and GABA. The main results highlight a synergistic interaction between the effects of acute L-Dopa and those driven by HFS. Indeed, it appears that HFS stimulation stabilizes dopamine contents increased by acute L-Dopa, delaying its metabolism. These results could then bring interesting arguments concerning the beneficial effects of STN HFS observed in PD patients, in particular regarding the stabilization of motor fluctuations.
Altogether, these data give new arguments for a better understanding of STN HFS mechanisms, and bring new prospects justifying the importance of STN HFS as a powerful treatment of PD.
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https://tel.archives-ouvertes.fr/tel-00152498
Contributor : Emilie Lacombe <>
Submitted on : Thursday, June 7, 2007 - 9:11:35 AM
Last modification on : Friday, November 6, 2020 - 4:05:02 AM
Long-term archiving on: : Thursday, April 8, 2010 - 7:08:31 PM

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  • HAL Id : tel-00152498, version 1

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Emilie Lacombe. MODIFICATIONS NEUROCHIMIQUES INDUITES PAR LA STIMULATION HAUTE FREQUENCE DU NOYAU SOUS-THALAMIQUE AU SEIN DES RESEAUX NEURONAUX IMPLIQUES DANS LES CIRCUITS MOTEURS ET LEURS INTERACTIONS AVEC UN TRAITEMENT A LA L-DOPA

Etude par microdialyse intracérébrale chez le rat sain et hémiparkinsonien.. Neurosciences [q-bio.NC]. Université Joseph-Fourier - Grenoble I, 2007. Français. ⟨tel-00152498⟩

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