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.