Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective
therapy for
Parkinson's disease; however, the mechanism whereby DBS ameliorates the symptoms of
Parkinson's disease remains an area of intense research. In the present study, we investigated the hypothesis that the
neurotransmitter glutamate is released within the STN during high-frequency stimulation (HFS) of the STN. Direct measurements of extracellular
glutamate concentration in the STN were made using a dual
enzyme-based electrochemical sensor. The studies were carried out in
ketamine/
xylazine anesthetized rats placed in a Kopf stereotaxic head frame. Various electrical stimulations (100-micros cathodic pulses; 100-3000 microA; 10- to 1000-Hz frequency; 5-s to 60-min stimulus durations) using bipolar stimulating
electrodes were delivered to the STN. Stimulation of the STN elevated the concentration of
glutamate in the STN. The concentration of
glutamate rose quickly during HFS, remained elevated for the duration of stimulation, and descended slowly towards baseline upon cessation of stimulation. Elevation of the extracellular concentration of
glutamate in the STN may be an important mechanism whereby DBS in the STN improves the symptoms of
Parkinson's disease. Furthermore, our data argue against the hypothesis that DBS works primarily by electrotonic inhibition of the stimulated structure.