TY - JOUR T1 - Modulation of Epileptiform Activity by Adenosine A1 Receptor-Mediated Mechanisms in the Juvenile Rat Hippocampus JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1412 LP - 1419 VL - 286 IS - 3 AU - Virginia Tancredi AU - Margherita D’Antuono AU - Astrid Nehlig AU - Massimo Avoli Y1 - 1998/09/01 UR - http://jpet.aspetjournals.org/content/286/3/1412.abstract N2 - The modulatory role played by purinergic mechanisms on the epileptiform discharges induced by 4-aminopyridine (4AP, 50 μM) in juvenile (10 to 25-day-old) rat hippocampal slices was studied with field potential recordings in the CA3 stratum radiatum. 4AP-induced activity consisted of interictal and ictal discharges along with isolated γ-aminobutyric acid-mediated potentials. The adenosine analogues 2-Cl-adenosine (10–200 μM) and N-ethylcarboxamido-adenosine (5–10 μM), the A1 receptor agonist N6-(L2-phenylisopropyl)-adenosine (2–10 μM), and the adenosine uptake inhibitor dipyridamole (1–40 μM) reduced and eventually abolished interictal and ictal discharges with IC50 values that were larger for ictal discharges as compared to interictal activity. These purinergic agents did not modify the rate of occurrence of the γ-aminobutyric acidmediated potentials recorded during application of excitatory amino acid receptor antagonists. The changes induced by 2-Cl-adenosine, N6-(L2-phenylisopropyl)-adenosine, or dypiridamole were reversed by caffeine (500 μM) or 8-cyclopentyl-1,3-dipropylxantine (100 μM). However, these adenosine receptor antagonists did not alter the epileptiform discharges induced by 4AP. The depressant effects induced by N6-(L2-phenylisopropyl)-adenosine on the epileptiform activity were maintained in the presence of barium (2 mM), which blocks adenosine postsynaptic actions. These results demonstrate that activation of adenosine A1 receptors in the juvenile rat hippocampus leads to an anticonvulsant action that can be ascribed to a decreased release of glutamate from CA3 pyramidal cell terminals. We also propose that during the first weeks of postnatal life endogenous adenosine does not activate A1 receptors to a degree to control the ability of hippocampal neurons to generate epileptiform activity in the 4AP model. The American Society for Pharmacology and Experimental Therapeutics ER -