Iontophoretic studies on rat hippocampus with some novel GABA antagonists |
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| Authors: | T Dalkara E Saederup R F Squires K Krnjevic |
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| Affiliation: | 1. Anaesthesia Research Department, McGill University 3655 Drummond Street Montreal, Quebec, Canada H3G 1Y6, USA;2. Present address: Institute of Pharmacology and Toxicology Hacettepe University Hacettepe, Ankara, Turkey;3. Nathan Kline Institute for Psychiatric Research Orangeburg, New York 10962, USA;1. Department of Physics, School of Sciences, Beihua University, Jilin, 132013, China;2. College of Physics and Electronic Information, Luoyang Normal University, Luoyang, 471022, China;1. Biological Sciences Division, Pritzker School of Medicine, University of Chicago, Chicago, Illinois;2. Department of Radiology, Feinberg School of Medicine, Northwestern University, 676 N. Saint Clair Street, Chicago, IL 60611;3. Department of Radiology, Section of Interventional Radiology, Chicago, Illinois;4. Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois |
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| Abstract: | Twelve substances which appear to be GABA antagonists, judging by their ability to reverse the inhibitory effect of GABA on 35S-TBPS binding to rat brain membranes, were tested iontophoretically on population spikes in the rat hippocampus. Eight of them, including seven which completely reversed the inhibitory action of GABA on 35S-TBPS binding, caused a marked enhancement of population spikes, with slow onset and long duration and they antagonized the inhibition of population spikes by GABA. These effects were similar to those produced by bicuculline. Electrophysiologically, the most potent of the "complete reversers" were bathophenanthroline disulfonate and brucine. In vitro, amoxapine and brucine most effectively reversed the inhibitory action of GABA on 35S-TBPS binding. Of the five substances which only partly reversed the inhibitory effect of GABA on 35S-TBPS binding, four depressed the population spikes and potentiated the inhibitory action of GABA. The fifth "partial reverser", pipazethate, potently increased the population spikes, like the "complete reversers". Although other interpretations are possible the results are consistent with the existence of several GABA-A receptor types in brain, only some of which are blocked by certain partial reversers. |
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