Modification of evoked hippocampal dentate inhibition by diazepam and three antagonists in urethane-anesthetized rats.
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 gamma-aminobutyric acid (GA-BAA)-mediated recurrent inhibition. The antagonist RO15-1788, but not CGS-8216 or PK-11195, also significantly increased early 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.
Albertson
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TE
Department of Internal Medicine and Pharmacology, School of Medicine, University of California, Davis 95616.
Joy
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RM
D000758:Anesthesia; D000818:Animals; D003975:Diazepam / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D005442:Flumazenil / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000502:physiology; D013569:Synapses / Q000502:physiology; D014520:Urethane; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D007546:Isoquinolines; D011720:Pyrazoles; D011963:Receptors, GABA-A; D014520:Urethane; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; D003975:Diazepam; C037850:PK 11195