Electrophysiological evidence for agonist properties of flumazenil, a benzodiazepine receptor antagonist, in rat hippocampus slices.

The purpose of this study was to determine the ability of the putative benzodiazepine antagonist flumazenil to modulate the excitatory synaptic responses recorded from rat hippocampus slices. The benzodiazepine agonist clonazepam was demonstrated to depress the CA1 population spike. This effect was attributed to an enhancement of GABA efficacy after its electrically-elicited release from local inhibitory circuitry. As an unexpected effect, flumazenil failed to antagonize this depressing effect. Moreover, flumazemil was observed to significantly depress, on its own, the magnitude of the evoked response to the activation of the excitatory afferents. This intrinsic depressant activity of flumazenil suggests that flumazenil acts 'in vitro' as an agonist at the benzodiazepine receptors, and is consistent with some previously reported atypical effects of flumazenil 'in vivo'.