Objective: Globus pallidus interna (GPi) is recognized as an effective treatment for advanced Parkinson’s disease. However, the neurochemical basis of its effects remains unknown. The aim of this study was to investigate effects of entopeduncular nucleus (EPN) stimulation, the equivalent to human GPi, in sham and 6-hydroxydopamine (6-OHDA)-lesioned rat model on changes of glutamate and GABA in the striatum.

Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopamine depletion due to the degeneration of substantia nigral dopamine neurons. Globus pallidus interna (GPi) stimulation has become an established treatment for motor symptoms of PD. However, the exact mechanism of deep brain stimulation (DBS) in GPi stimulation is unknown.

Method: Extracellular glutamate and GABA level changes in striatum of sham group, sham plus deep brain stimulation (DBS) group, 6-OHDA group, and 6-OHDA plus DBS group were examined using microdialysis and high-pressure liquid chromatography (HPLC). Tyrosine hydroxylase (TH) immunoreactivities in substantia nigra and striatum of the four groups were also analyzed.

Results: Extracellular glutamate levels in the striatum of sham plus DBS group and 6-OHDA plus DBS group were significant increased by EPN stimulation compared to those in the sham group and 6-OHDA group. However, extracellular GABA levels of the striatum of sham plus DBS group and 6-OHDA plus DBS group had no significant changes by EPN stimulation compared to those in the sham group and 6-OHDA group. EPN stimulation had no significant effect on the expression of tyrosine hydroxylase in sham or 6-OHDA group.

Conclusion: Our results provided new neurochemical data of EPN stimulation. Clinical results of EPN stimulation are not restricted to direct inhibitory outflow to thalamus. They also involve widespread adaptive changes within the basal ganglia.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/change-of-extracellular-glutamate-and-gaba-level-in-striatum-during-deep-brain-stimulation-of-the-entopeduncular-nucleus-in-rats/