Benzodiazepine inverse agonists augment long-term potentiation in CA1 and CA3 of guinea pig hippocampal slices.
The effects of benzodiazepine inverse agonists on the long-term potentiation of synaptic transmission in hippocampal slices of the guinea pig were examined using an extracellular recording technique. Benzodiazepine inverse agonists, beta-carboline-3-carboxylate (beta-CCE), 2-phenylpyrazolo [4,3-c]quinolin-3(5H)-one (CGS-8216) and 2-[5-methylthien-3-yl]-2,5-dihydro-3H-pyrazolo [4,3-c]quinolin-3-one (S-135), augmented the magnitude of long-term potentiation induced by tetanic stimulation of input fibers in both the CA1 and the CA3 regions. beta-Carboline-3-carboxylate was more effective in augmenting long-term potentiation in CA1 than in CA3. Augmentation of long-term potentiation produced by beta-CCE was antagonized by concomitant application of flumazenil, a benzodiazepine receptor antagonist. Therefore, the enhancing action of benzodiazepine inverse agonists on long-term potentiation, which is suggested to be a specific action, mediated by the GABA/benzodiazepine receptor complex, might help to explain the mechanism of the memory-enhancing effects of benzodiazepine inverse agonists, observed in some in vivo behavioral paradigms.
Department of Pharmacology, Shionogi Research Laboratories, Shionogi & Co. Ltd, Osaka, Japan.
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M
Yasui
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K
Kawasaki
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A
Matsushita
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M
Satoh
D000818:Animals; D001569:Benzodiazepines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002243:Carbolines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005442:Flumazenil / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D011619:Psychotropic Drugs / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology
D002243:Carbolines; D011619:Psychotropic Drugs; D011720:Pyrazoles; D015363:Quinolones; C059074:S 135; D001569:Benzodiazepines; D005442:Flumazenil; C024915:beta-carboline-3-carboxylic acid ethyl ester; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one