Control of 4-aminopyridine-induced synchronous activity by adenosine A1 and mu-opioid receptor agonists in adult rat hippocampus.

In the presence of 4-aminopyridine (4AP, 50 microM) two types of spontaneous field potentials can be recorded in the CA3 stratum radiatum of adult rat hippocampal slices. First, epileptiform interictal discharges (0.85 +/- 0.25 Hz) that are blocked by excitatory amino acid ionotropic receptor antagonists. Second, negative-going synchronous potentials (0.036 +/- 0.015 Hz) which are solely abolished by application of bicuculline methiodide (BMI). Bath application of the specific adenosine A1 receptor agonist, N6-(L-2-phenylisopropyl) adenosine (L-PIA), reduced the frequency of interictal discharges in a dose-dependent manner (IC50 = 8.75 microM; n = 9 slices) and this effect was reversed by the specific adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 microM; n = 3 slices). L-PIA did not affect the frequency of occurrence of the negative-going field potential during application of excitatory amino acid receptor antagonists. This BMI-sensitive event was depressed, however, by application of the mu-opioid receptor agonist [D-Ala2-N-Me-Phe4,Gly5(5)-ol]enkephalin (DAGO, 10 microM; 15.1 +/- 8.7% of rate in control; n = 6 slices), an effect that was antagonized by naloxone (20 microM). Our results indicate that L-PIA reduces the 4AP-induced epileptiform activity through the activation of adenosine A1 receptors. This procedure does not influence the BMI-sensitive field potential, which is abolished, however, by DAGO. Thus, our findings support the hypothesis that the BMI-sensitive potential is due to the presynaptic release of GABA from interneurons.