GABA outflow is modulated by electrical high frequency pulses during N-methyl-D-aspartate receptor activation in the rat caudate nucleus

GABAergic neurons have been demonstrated to play an essential role in the mechanism of high frequency stimulation of deep brain regions, which is an effective treatment in Parkinson's disease. In this study, the effects of electrical high frequency (hf)-pulses and N-methyl-D-aspartate (NMDA) receptor activation on GABA and glutamate outflow were examined in slices of the rat caudate nucleus. Therefore, superfusion experiments were performed and GABA and glutamate outflow were measured by means of HPLC with electrochemical detection after pre-column derivatisation with o-phthaldialdehyde sulphite.

After a 40min washout period, basal transmitter outflow was measured in four 10min fractions. The NMDA agonist RS – tetrazol –5yl – glycine (RS-TG, 10µM) and hf-pulses (130Hz, 600µA, 60µs each pulse) were applied for a 10min period. Addition of RS-TG had no effect on GABA outflow in presence of magnesium ions (MgSO4, 1.10 mM) in the superfusion medium. Under these conditions, application of hf-pulses did not modify GABA outflow. When experiments were performed in absence of magnesium, RS-TG was able to induce an increase of GABA outflow from basal values (2.73±0.34 nM=100%) to 4.58±0.96 nM (=168%). As the most outstanding result, simultaneous hf-pulses decreased the RS-TG-induced effect on GABA outflow from 168 to 121% compared to basal. In all experiments, no significant modifications of glutamate outflow could be observed.

In conclusion, we could demonstrate NMDA receptor-mediated activation of GABAergic neurons in absence of extracellular magnesium in slices of the rat caudate nucleus. The inhibitory effect of hf-pulses on NMDA-evoked GABA outflow without modulation of glutamate outflow led us to suggest specific effects on GABAergic neurons in the mechanism of action of high frequency stimulation.