Involvement of the adenosine neuromodulatory system in the benzodiazepine-induced depression of excitatory synaptic transmissions in rat hippocampal neurons in vitro

We investigated whether adenosine neuromodulation is involved in a benzodia zepine (midazolam)-induced depression of excitatory synaptic transmissions in the CA1 and dentate gyrus (DG) regions in rat hippocampal slices. Field excitatory postsynaptic potentials (fEPSPs), evoked by electrical stimulati on of the CA1-Schaffer collateral or the DG-perforant path, were recorded w ith extracellular microelectrodes from CA1-stratum radiatum or DG-stratum m oleculare in oxygenated ACSF. The initial slope of the fEPSPs was analyzed for assessing the drug effects. Midazolam (1 mu M) transiently depressed CA 1- and DG-fEPSPs. The fEPSPs were depressed to approximately 75% of the con trol values, and then gradually recovered. The depression was not affected by bicuculline, a GABAA receptor antagonist, although it was completely ant agonized by aminophylline, an adenosine receptor antagonist. Dipyridamole ( 5 mu M), an adenosine uptake inhibitor, depressed the fEPSPs in a similar m anner to midazolam. An adenosine deaminase inhibitor, EHNA, also transientl y depressed the fEPSPs, but in a different manner. Exogenous adenosine pers istently depressed the fEPSPs. The effects of the drugs were not significan tly different in the CA1 and DG regions. The results suggest that midazolam (1 mu M) depresses excitatory synaptic transmissions through the adenosine neuromodulatory system by inhibiting adenosine uptake in the CA1 and DG re gions of the hippocampus. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.