Urethane-anesthetized rats with perforant pathway stimulating electrodes and recording electrodes placed in the hippocampal dentate gyrus were exposed to increasing doses of either the benzodiazepine agonist diazepam or an antagonist (PK-11195, CGS-8216, and RO15-1788). Analysis of the monosynaptic evoked field potentials indicated that none of the four compounds altered the threshold for eliciting the excitatory postsynaptic potential (EPSP). Reductions in field population spike (PS) amplitudes were seen after exposure to RO15-1788, CGS-8216, and diazepam, but not PK-11195. Using a paired-pulse paradigm, diazepam significantly increased early γ-aminobutyric acid (GAbAA)-mediated recurrent inhibition. The antagonist RO15-1788, but not CGS-8216 or PK-11195, also significantly increased aerly GABAA-mediated inhibition. The increase in GABAA-mediated inhibition after diazepam was reversed by the subsequent administration of the central antagonists RO15-1788 or CGS-8216, but not the peripheral antagonist PK-11195. Pretreatment with CGS-8216 or RO15-1788 prevented diazepam-induced inhibition. These data support the important modulatory role of the central benzodiazepine receptor in early GABAA-mediated inhibition at this synapse. They also suggest that basal granule cell excitability is not importantly modulated by this benzodiazepine receptor.
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