Endogenous adenosine induces NMDA receptor-independent persistent epileptiform discharges in dorsal and ventral hippocampus via activation of A2 receptors

Summary: Although adenosine is widely assumed to be an endogenous anticonvulsant its role in epileptogenesis is still contradictory. Using slices from the dorsal (DH) and the vental (VH) rat hippocampus and extracellular recordings from the CA3 field we aimed to determine the effects of endogenous adenosine on the expression and long-term maintenance of epileptiform activity induced by blockade of adenosine receptors types A1 (A1R) and A2 (A2R) under conditions of low magnesium. We found that the A1Rs blockade induced persistent epileptiform discharges (PED) more frequently in VH (by 52%) than in DH (by 31%). The induction of PED upon an additional blockade of A2Rs increased in VH (by 48%) but decreased in DH (by 74%). Remarkably, the increment in VH was prevented by a blockade of NMDARs. A blockade of A2Rs increased the NMDAR-mediated component of evoked synaptic potential in both VH and DH (by ∼100%) but suppressed the non-NMDAR-mediated component in DH but not VH. A blockade of A1Rs induced PED equally in DH (76%) and VH (80%) via a NMDAR-independent mechanism. A blockade of A2Rs under blockade of A1Rs and NMDARs reduced the PED to 17% in DH and to 38% in VH. These findings show that A2Rs play a different role in the long-term maintenance of epileptiform activity between DH and VH and suggest that endogenous activation of A2Rs facilitates NMDAR-independent induction of PED in both hippocampal poles, but suppresses NMDAR-dependent induction of PED in VH. [ABSTRACT FROM AUTHOR]