Deep brain stimulation: Response to neuronal high frequency stimulation is mediated through GABAA receptor activation in rats

High frequency stimulation (HFS) of deep brain regions such as globus pallidus internus or subthalamic nucleus can reverse Parkinson's symptoms probably through activation of γ-aminobutyric acid (GABA)ergic neurotransmission. To prove the hypothesis, rat striatal slices were stimulated electrically (130 Hz) in vitro and dopamine (DA) outflow was measured using high performance liquid chromatography. HFS induced an attenuation in basal DA release in perfusate. Veratridine-induced DA outflow was blocked by the simultaneous application of HFS. Addition of bicuculline, a GABA_A receptor antagonist, reversed the effect of HFS on DA outflow. In addition, destruction of striatal GABAergic neurons with kainic acid also reversed the effect of HFS. In conclusion, our present data provide strong evidence that HFS does not only need presynaptic GABA_A receptors but also intact GABAergic nerve terminals coupled to GABA_A receptors to exert an inhibitory effect and give a rationale of HFS effectiveness in the treatment of Parkinson's disease.