Regional differences in the depressant effects of midazolam on excitatory synaptic transmission in the rat hippocampus

Abstract

The effects of midazolam, one of the most popular benzodiazepines, was examined on excitatory synaptic transmission in the hippocampus. Both CA1 pyramidal cells (CA1-PCs) and dentate gyrus granule cells (DG-GCs) were studied in rat hippocampal slices with extracellular recordings. Midazolam depressed the amplitudes of orthodromic population spikes (O-PS) and excitatory postsynaptic potential (EPSP) slopes of CA1-PCs in a dose-dependent manner, but depressed those of DG-GCs to a lesser extent. On the other hand, midazolam had little effect on the amplitudes of antidromic population spikes of both CA1-PCs and DG-GCs. A GABAA receptor antagonist bicuculline strongly antagonized the depressant effects of 75 microM midazolam on the amplitudes of O-PS by 73% in CA1-PCs, whereas it did not antagonize the effects of midazolam in DG-GCs. These results suggest that the differential effects of midazolam could be due to the different types and/or density of GABAA receptors between CA1-PCs and DG-GCs.