Deep brain stimulation: response to neuronal high frequency stimulation is mediated through GABA(A) 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 gamma-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.
Moser
Andreas
A
Department of Neurology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. moser_a@neuro.mu-luebeck.de
Gieselberg
Annabella
A
Ro
Bora
B
Keller
Christine
C
Qadri
Fatimunnisa
F
D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*
D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D004298:Dopamine