Antiepileptic effects of GABAb receptor activation in area CA3 of rat hippocampus.
The role of GABAb receptor activation in the expression of both interictal and ictal phenomena was investigated in slices of area CA3 of the rat hippocampal formation. Interictal-like bursts occurred following application of high frequency trains to the Schaffer collaterals. When two bursts were triggered using paired stimuli, profound depression of the second burst was seen 150-600 ms following the first burst. GABAb receptor antagonists potently reversed the paired pulse depression of the interictal-like bursts. Reversal of the paired depression was also accomplished by increasing the extracellular concentration of K+ by 2-3 mM. Additional experiments were performed in area CA3 to determine the role of GABAb receptor activation on the expression of ictal phenomena. Electrographic seizures (EGSs) were induced by application of high frequency trains. 2-Hydroxy-saclofen (200 microM) significantly decreased the duration of trains required to elicit EGSs. Taken together, these data suggest that GABAb receptor activation has potent inhibitory effects on both ictal and interictal-like events.
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260.
R A
RA
Morrisett
D V
DV
Lewis
H S
HS
Swartzwelder
W A
WA
Wilson
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004558:Electric Stimulation; D004569:Electroencephalography; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011712:Pyramidal Tracts / Q000166:cytology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*
D000927:Anticonvulsants; D058787:GABA-A Receptor Antagonists; D015221:Potassium Channels; D011963:Receptors, GABA-A; D011188:Potassium