MODULATION OF EPILEPTIFORM ACTIVITY BY ADENOSINE-A1 RECEPTOR-MEDIATEDMECHANISMS IN THE JUVENILE RAT HIPPOCAMPUS

The modulatory role played by purinergic mechanisms on the epileptifor m discharges induced by 4-aminopyridine (4AP, 50 mu M) in juvenile (10 to 25-day-old) rat hippocampal slices was studied with field potentia l recordings in the CA3 stratum radiatum. 4AP-induced activity consist ed of interictal and ictal discharges along with isolated gamma-aminob utyric acid-mediated potentials. The adenosine analogues 2-Cl-adenosin e (10-200 mu M) and N-ethylcarboxamido-adenosine (5-10 mu M), the Al r eceptor agonist N-6-(L2-phenylisopropyl)-adenosine (2-10 mu M), and th e adenosine uptake inhibitor dipyridamole (1-40 mu M) reduced and even tually 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 g amma-aminobutyric acid-mediated potentials recorded during application of excitatory amino acid receptor antagonists. The changes induced by 2-Cl-adenosine, N-6-(L2-phenylisopropyl)-adenosine, or dypiridamole w ere reversed by caffeine (500 mu M) or 8-cyclopentyl-1,3-dipropylxanti ne (100 mu M). However, these adenosine receptor antagonists did not a lter the epileptiform discharges induced by 4AP. The depressant effect s induced by N-6-(L2-phenylisopropyl)-adenosine on the epileptiform ac tivity were maintained in the presence of barium (2 mM), which blocks adenosine postsynaptic actions. These results demonstrate that activat ion of adenosine Al 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 d uring the first weeks of postnatal life endogenous adenosine does not activate Al receptors to a degree to control the ability of hippocampa l neurons to generate epileptiform activity in the 4AP model.