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

Abstract

In the presence of 4-aminopyridine (4AP, 50 μM) 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 A 1 receptor agonist, N 6-( l -2- phenylisopropyl) adenosine ( l-PIA), reduced the frequency of interictal discharges in a dose-dependent manner (IC 50 = 8.75 μM; n = 9 slices) and this effect was reversed by the specific adenosine A 1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 μM; 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 μ-opioid receptor agonist [ d-Ala 2-N- Me-Phe 4 , Gly5 5-ol]enkephalin (DAGO, 10 μM; 15.1 ± 8.7% of rate in control; n = 6 slices), an effect that was antagonized by naloxone (20 μM). Our results indicate that l-PIA reduces the 4AP-induced epileptiform activity through the activation of adenosine A 1 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.