High-Frequency Stimulation of the Subthalamic Nucleus Potentiates l-DOPA-Induced Neurochemical Changes in the Striatum in a Rat Model of Parkinson's Disease

Mechanisms of High Frequency Stimulation of the Subthalamic Nucleus in Parkinson's Disease: From Local to Distal Effects on the Basal Ganglia Network

“…The authors suggested that this stabilization of striatal DA concentrations may be involved in the alleviation of levodoparelated motor fluctuations, such as the wearing-off phenomenon in particular (Nimura et al, 2005), as De la Fuente-Fernandez et al, (de la Fuente-Fernandez et al, 2001) showed that fluctuations in striatal synaptic DA concentrations precede the clinically apparent wearingoff phenomenon. Another study in 6-OHDA-treated awake rats demonstrated that STN-HFS did not alleviate and might even have prolonged LID and exacerbated LID-associated changes in the levels of several striatal markers, such as preproenkephalin (PPE) and preprodynorphin (PPDyn) mRNA (Oueslati et al, 2007). Despite the apparent difference in these results, STN-HFS potentiates the effects of levodopa rather than counteracting the modifications induced by dopaminergic treatment in both cases.…”

“…As STN-HFS allows two of these factors -high doses and the pulsatile administration of levodopa and dopaminergic agonists -to be significantly reduced, it would be interesting to determine whether the decrease in LID expression induced by STN-HFS reflects direct and specific functional effects of stimulation on the BG network or an indirect action associated with a decrease in the daily dose of levodopa. Indeed, paradoxically, given the decrease in LID observed after stimulation, STN-HFS may have a dyskinesia-inducing effect in some patients (Krack et al, 2003;Limousin et al, 1996;Volkmann et al, 2001) and in animal models of the disease (Boulet et al, 2006;Oueslati et al, 2007) if the voltage is increased, emphasizing the complex interactions between levodopa treatment and STN-HFS. Several recent experimental studies have provided strong evidence that the striatum is a primary site of interaction between levodopa and STN-HFS (Gubellini et al, 2006;Lacombe et al, 2007;Oueslati et al, 2007).…”

“…Indeed, paradoxically, given the decrease in LID observed after stimulation, STN-HFS may have a dyskinesia-inducing effect in some patients (Krack et al, 2003;Limousin et al, 1996;Volkmann et al, 2001) and in animal models of the disease (Boulet et al, 2006;Oueslati et al, 2007) if the voltage is increased, emphasizing the complex interactions between levodopa treatment and STN-HFS. Several recent experimental studies have provided strong evidence that the striatum is a primary site of interaction between levodopa and STN-HFS (Gubellini et al, 2006;Lacombe et al, 2007;Oueslati et al, 2007). A microdialysis study on anesthetized rats with partial DA depletion showed that STN-HFS interacts synergically with levodopa-induced changes in striatal extracellular DA concentration, by stabilizing the levodopa-induced increase in striatal DA levels ( Fig.…”

Deep Brain Stimulation of the Center Median-Parafascicular Complex of the Thalamus Has Efficient Anti-Parkinsonian Action Associated with Widespread Cellular Responses in the Basal Ganglia Network in a Rat Model of Parkinson's Disease

“…The material and procedure for the stimulation were the same as previously used for STN-HFS (Oueslati et al, 2007). The stimulating electrode was formed by two parallel platinum iridium wires insulated with Teflon and bared at the extremity on a length of 500 m (diameter of each wire; insulated, 140 m; bare, 76 m).…”

Evaluation of Metabolic State in Striatal Rat Model of Parkinson’s Disease: before and after Deep Brain Stimulation

“…To investigate the additional effect of DBS in the 6-OHDA striatal rat model of PD a model of electrode implantation and of bilateral high frequency stimulation at the level of the STN was used [17,32,42]. Insertion of the electrodes did not cause any significant changes in the metabolic parameters tested, therefore ruling out any effect on structures others than the ones being targeted by stimulation.…”