Abstract：
:Electrical high frequency deep brain stimulation (DBS) of the globus pallidus internus (GPi) or the subthalamic nucleus (STN) has dramatic beneficial motor effects in advanced Parkinson's disease (PD). However, the mechanisms underlying these clinical results remain unclear. It is proposed that the gamma-aminobutyric acid (GABA) system is involved in the effectiveness of DBS. To prove this hypothesis, rat striatal slices were stimulated electrically (130 Hz) in vitro; GABA and glutamate (GLU) outflow from striatal slices of normal or kainic acid-lesioned rats were measured after o-phthaldialdehyde sulphite derivatization using HPLC with electrochemical detection. Our results could demonstrate that high frequency stimulation (HFS) did not modulate basal GABA outflow in the perfusate. In the presence of submaximal concentrations of the voltage-gated sodium channel opener veratridine, HFS significantly enhanced GABA outflow. When the GABA transporter inhibitor, nipecotic acid, was added to the incubation medium, the HFS effects decreased to nearly control values. Destruction of striatal GABAergic neurons by kainic acid completely reversed the effects of HFS on GABA outflow. In the present study no effect of HFS on glutamate outflow was observed under any condition. These results suggest that HFS has a specific effect on GABAergic neuronal terminals resulting in an enhancement of extracellular GABA in the caudate nucleus. This effect is probably due to an inhibitory effect of HFS on the GABA uptake system rather than to stimulation of vesicular GABA release from GABAergic neurons, which are both associated with the presynaptic GABAergic physiology.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Li T,Qadri F,Moser Adoi
10.1016/j.neulet.2004.08.050keywords:
subject
Has Abstractpub_date
2004-11-23 00:00:00pages
117-21issue
2-3eissn
0304-3940issn
1872-7972pii
S0304-3940(04)01060-2journal_volume
371pub_type
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