In this study the role of adenosine A(1) and A(2A) receptors of the hippocampal. CA1 region on piriform cortex-kindled seizures was investigated in rats. Animals were kindled by daily electrical stimulation of piriform cortex. In fully kindled rats, N-6-cycohexyladenosine (CHA; a selective A, receptor agonist), 1,3dimethyl-8-cyclopenthytxanthine (CPT, a selective A, receptor antagonist), CGS21680(2A) receptor agonist) and, ZM241385 (ZM, a selective hydrochloride (CGS, a selective A A2A receptor antagonist) were microinfused bilaterally into the hippocampal CA1 region. Rats were stimulated and seizure parameters were measured. Obtained results showed that microinjection of CHA (10 and 100 mu M) decreased the afterdischarge duration (ADD), stage 5 seizure duration (S5D) and seizure duration (SD), and significantly increased the latency to stage 4 (S4L). Intra-hippocampal CPT increased ADD at the dose of 20 mu M. Pretreatment of rats with CPT (10 PM) before CHA (10 mu M), significantly reduced the effect of CHA on seizure parameters. On the other hand, microinjection of CGS (200 and 500 mu M) increased ADD, but of ZM had no effect on seizure parameters. Pretreatment of rats with ZM (50 mu M) before CGS (500 mu M), significantly reduced the effect of CGS on seizure parameters. The results suggest that the facititatory role of the hippocampat CA1 region in relaying or spreading of piriform cortex kindled seizures is decreased by the activation of adenosine A(1) receptors and increased by A(2A) receptors. (c) 2006 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.