Electrically evoked GABA release in rat hippocampus CA1 region and its changes during kindling epileptogenesis.
Previous findings on changes in K+-induced GABA release from hippocampal slices during kindling epileptogenesis were reinvestigated using physiological electrical stimulation. For that purpose, a procedure was developed enabling neurochemical monitoring of GABA release locally in the CA1 region of rat hippocampal slices upon tetanic stimulation of Schaffer-collateral fibers. In the presence of a GABA reuptake blocker, subsequent application of short (3 s) pulses of 50-Hz stimuli induced a local transient increase in GABA release. In slices from fully kindled animals, 24 h after the last generalized seizure, tetanically stimulated GABA release was increased in comparison to control slices. In slices from long-term kindled animals, 4-5 weeks after the last seizure, tetanically stimulated GABA release had returned to control levels. Application of the broad low-affinity GABAB receptor antagonist saclofen increased the tetanically stimulated GABA release in control slices, but had no effect in fully kindled slices. In slices from long-term kindled animals, however, saclofen enhanced GABA release similarly as in control slices. We conclude that the transient increase in tetanus-induced GABA release during kindling epileptogenesis is seizure-related, and probably caused by temporarily impaired presynaptic GABAB receptors. The possible relevance of this finding for GABA transmission in epilepsy is discussed.
Ghijsen
Wim E J M
WE
Swammerdam Institute for Life Sciences, Centre for Neuroscience, University of Amsterdam, Kruislaan 320, 1090 GB Amsterdam, The Netherlands. ghijsen@science.uva.nl
Zuiderwijk
Mark
M
Lopes da Silva
Fernando H
FH
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage; D001418:Baclofen / Q000008:administration & dosage / Q000031:analogs & derivatives; D004558:Electric Stimulation / Q000009:adverse effects*; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology*; D018756:GABA Antagonists / Q000008:administration & dosage; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D066298:In Vitro Techniques; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D009557:Nipecotic Acids / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000927:Anticonvulsants; D018756:GABA Antagonists; D009557:Nipecotic Acids; D005680:gamma-Aminobutyric Acid; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid; D001418:Baclofen; C080629:saclofen