Adenosine inhibits epileptiform activity arising in hippocampal area CA3

Abstract

1 The ability of adenosine and structurally-related compounds to inhibit epileptiform activity induced by bicuculline in the CA3 region of the hippocampal slice of the rat was examined. 2 Bath application of all purinoceptor agonists tested reduced the frequency of generation of burst potentials. Analysis of dose-response curves yielded the following IC₅₀ values: adenosine, 1.5 μm; 2-chloroadenosine, 0.144 μm; 5′-(N-ethyl)carboxamidoadenosine, 30.2 nm; L-phenylisopropyladenosine, 12.1 nm; cyclohexyladenosine, 7.9 nm. 3 Theophylline (30 μm) increased the rate of bursting and antagonized the effect of exogenous adenosine. 4 Dipyridamole (0.03–1 μm) reduced the occurrence of burst firing. 5 In slices untreated with bicuculline, theophylline (30 μm) and adenosine deaminase (10 μg ml⁻¹) induced bursting activity. 6 These results demonstrate that purinoceptor agonists can suppress epileptiform activity in the hippocampus and suggest that adenosine may act as an endogenous anticonvulsant.