RT Journal Article SR Electronic T1 Epileptiform Synchronization and GABAB Receptor Antagonism in the Juvenile Rat Hippocampus JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1102 OP 1113 DO 10.1124/jpet.102.040782 VO 303 IS 3 A1 Rita Motalli A1 Margherita D'Antuono A1 Jacques Louvel A1 Irene Kurcewicz A1 Giovanna D'Arcangelo A1 Virginia Tancredi A1 Mario Manfredi A1 René Pumain A1 Massimo Avoli YR 2002 UL http://jpet.aspetjournals.org/content/303/3/1102.abstract AB The GABAB receptor agonist baclofen enhances the epileptiform activity induced by 4-aminopyridine (4AP) in juvenile rat hippocampal slices. In this study, we used a similar experimental approach (i.e., field potential, intracellular, and [K+]o recordings in the CA3 area of slices obtained from 15–23-day-old rats) to establish whether antagonizing GABAB receptors could exert opposite (presumably anticonvulsant) effects. Bath application of 4AP (50 μM) induced spontaneous interictal and ictal discharges along with synchronous GABA receptor-mediated potentials. All types of 4AP-induced synchronous activity occurred more frequently during application of the GABAB receptor antagonistp3-amino-propyl,p-diethoxymethylphosphonic acid (CGP 35348) (0.1–1 mM; EC50 = 0.25 mM). Moreover, CGP 35348 augmented the frequency and, to a lesser extent, the duration of the asynchronous synaptic activity recorded intracellularly from CA3 pyramids (n = 19). In medium containing 4AP + ionotropic glutamatergic antagonists (which abolished interictal and ictal activity), CGP 35348 prolonged both GABA-receptor-mediated field potentials and the accompanying intracellular long-lasting depolarizations without modifying their rate (n = 12). The transient elevations in [K+]o associated with GABA receptor-mediated potentials in 4AP-containing medium (n = 7 slices) became larger during CGP 35348 application. Similar findings were obtained when CGP 35348 was applied to medium containing 4AP + ionotropic glutamatergic antagonists (n = 6). Thus, the effect of CGP 35348 on 4AP-induced epileptiform activity is not anticonvulsant and to some extent similar to what was reported in this model during GABAB receptor activation. We propose that the facilitation of ictal activity by CGP 35348 is mainly caused by the blockade of presynaptic GABAB receptor, leading to an increase in GABA release and subsequent larger [K+]o elevations.