THE SITE AND MECHANISM OF ACTION OF BENZODIAZEPINE IN RABBIT HIPPOCAMPUS

The purpose of this study was to determine the effects of benzodiazepine in area CA1 of the hippocampus, and to explore possible mechanisms of action for these agents in this brain area. Two distinctly different benzodiazepine-induced changes in hippocampal physiology have been identified. First, benzodiazepine depresses the population spike recorded in stratum pyramidale, indicating a decrease in action potential generation. Second, benzodiazepine decreases the magnitude of post-tetanic potentiation of the population EPSP recorded in stratum radiatum, and shortens the duration. The effect of benzodiazepine on pyramidal cell excitation was reversed by the GABA antagonis bicuculline, and mimicked by GABA itself. Thus the available evidence is consistent with the hypothesis that benzodiazepine acts by enhancing the effect of GABA in this area. In stratum radiatum, on the other hand, the effect of benzodiazepine on post tetanic potentiation of the population EPSP was not altered by bicuculline although bicuculline did antagonize GABA in this area. In addition, application of GABA, while it caused profound changes in the population EPSP,p, did not cause the same changes that were induced by benzodiazepine. Thus the evidence does not support the hypothesis that benzodiazepine is acting in stratum radiatum by enhancing the effects of GABA. ^