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 benzodiazepine (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 stimulation of the CA1-Schaffer collateral or the DG-perforant path, were recorded with extracellular microelectrodes from CA1-stratum radiatum or DG-stratum moleculare in oxygenated ACSF. The initial slope of the fEPSPs was analyzed for assessing the drug effects. Midazolam (1 microM) transiently depressed CA1- and DG-fEPSPs. The fEPSPs were depressed to approximately 75% of the control values, and then gradually recovered. The depression was not affected by bicuculline, a GABAA receptor antagonist, although it was completely antagonized by aminophylline, an adenosine receptor antagonist. Dipyridamole (5 microM), an adenosine uptake inhibitor, depressed the fEPSPs in a similar manner to midazolam. An adenosine deaminase inhibitor, EHNA, also transiently depressed the fEPSPs, but in a different manner. Exogenous adenosine persistently depressed the fEPSPs. The effects of the drugs were not significantly different in the CA1 and DG regions. The results suggest that midazolam (1 microM) depresses excitatory synaptic transmissions through the adenosine neuromodulatory system by inhibiting adenosine uptake in the CA1 and DG regions of the hippocampus.
Narimatsu
E
E
Department of Physiology, Sapporo Medical University School of Medicine, Hokkaido, Japan. enarimat@sapmed.ac.jp
Aoki
M
M
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000037:antagonists & inhibitors / Q000502:physiology*; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology; D004176:Dipyridamole / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008874:Midazolam / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology*
D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D018377:Neurotransmitter Agents; D058915:Purinergic P1 Receptor Antagonists; D001569:Benzodiazepines; D000628:Aminophylline; C010192:9-(2-hydroxy-3-nonyl)adenine; D004176:Dipyridamole; D000225:Adenine; D000241:Adenosine; D008874:Midazolam; D001640:Bicuculline