Modulation by GABAB receptors of spontaneous synchronous activities induced by 4-aminopyridine in the rat hippocampus.
Field potential recordings were made in the CA3 and/or CA1 subfields of rat hippocampal slices maintained in vitro during perfusion with medium containing the convulsant drug 4-aminopyridine (4AP, 50 microM). In this experimental condition, spontaneous interictal epileptiform discharges caused by the activation of excitatory amino acid receptors and synchronous, GABA-mediated potentials occurred regularly in both areas. Interictal discharges and GABA-mediated potentials were reduced and eventually abolished in both subfields by bath application of baclofen (0.5-100 microM), which is a selective agonist for the GABAB receptor. However, interictal epileptiform events disappeared in the presence of baclofen concentrations (i.e., 4.75 +/- 0.7 microM; IC50 = 3.4 microM; n = 9) that were lower than those required for abolishing the GABA-mediated potential (i.e., 96.1 +/- 19.4 microM; IC50 = 9.8 microM; n = 12). The effects of baclofen were antagonized by the GABAB receptor antagonists saclofen (1 mM; n = 3 slices) or CGP 35348 (0.2-1 mM; IC50 = 240 microM; n = 12 slices). Our findings indicate that activation of GABAB receptors by baclofen inhibits both types of 4AP-induced activities in the rat hippocampus although epileptiform discharges appear to be more sensitive than GABA-mediated potentials to this pharmacological procedure. Although our data do not indicate whether the action of baclofen is pre- or postsynaptic, they demonstrate that this mechanism is sensitive to available GABAB receptor antagonists.
Siniscalchi
A
A
Montreal Neurological Institute, Que., Canada.
Avoli
M
M
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000503:physiopathology; D005071:Evoked Potentials / Q000187:drug effects; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D058787:GABA-A Receptor Antagonists; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D015761:4-Aminopyridine; D001418:Baclofen