Effects of some GABA and NMDA antagonists on a model of presynaptic hippocampal paired pulse inhibition.
1. The effects of some NMDA antagonists (7-chlorokynurenic acid and CGS 19755) and of the GABA antagonist penicillin were tested in a model of presynaptic short-term paired-pulse inhibition elicited in rat hippocampal slice with high (+ 2 mM) calcium solutions subjected to paired (15 ms)-pulse stimulation paradigm. 2. In control condition a 15 ms paired-pulse stimulation delivered at the level of stratum radiatum, as revealed by the ratio between amplitudes of the conditioned and unconditioned CA1 population spikes (R2/R1), ranging from 1.27 to 2.57, a clear paired-pulse facilitation occurred. Slice perfusion with high (+ 2 mM) calcium shifted, within 30 min, as revealed by a significant (P<0.01) decrease in R2/R1 ratio, paired-pulse facilitation into inhibition. Further perfusion together to high (+ 2 mM) calcium with 0.5 mM penicillin or with 50 microM CGS 19755, but not with 50 microM 7-chlorokynurenic acid significantly decreases the degree of paired-pulse inhibition as revealed by a significative increase in the R2/R1 ratio. 3. The data, demonstrating an inhibitory influence of specific NMDA antagonists in a model a presynaptic paired-pulse inhibition, were discussed in relation with the specific psychodysleptic effects elicited by the drugs in animals and humans.
Sagratella
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Laboratorio di Farmacologia, Istituto Superiore di Sanità Roma, Italy.
Marinelli
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D000818:Animals; D015220:Calcium Channels; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D010406:Penicillins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D015220:Calcium Channels; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010406:Penicillins; D017661:Receptors, Presynaptic; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid