In this study the role of adenosine A1 and A2A 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, N6-cyclohexyladenosine (CHA; a selective A1 receptor agonist), 1,3-dimethyl-8-cyclopenthylxanthine (CPT; a selective A1 receptor antagonist), CGS21680 hydrochloride (CGS, a selective A2A receptor agonist) and, ZM241385 (ZM, a selective 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 microM) 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 microM. Pretreatment of rats with CPT (10 microM) before CHA (10 microM), significantly reduced the effect of CHA on seizure parameters. On the other hand, microinjection of CGS (200 and 500 microM) increased ADD, but of ZM had no effect on seizure parameters. Pretreatment of rats with ZM (50 microM) before CGS (500 microM), significantly reduced the effect of CGS on seizure parameters. The results suggest that the facilitatory role of the hippocampal CA1 region in relaying or spreading of piriform cortex kindled seizures is decreased by the activation of adenosine A1 receptors and increased by A2A receptors.

226Temporal lobe epilepsy is the most common disorder in adults and can be very difficult to manage in some patients.1 Kindling is one of the most commonly used animal models of temporal lobe epilepsy which has been used for preclinical evaluation of antiepileptic drugs.2 Kindling is the process by which repeatedly induced seizures result in an increasing seizure duration and enhanced behavioral involvement of those induced seizures. It is usually carried out by focal electrical stimulation of the brain. With repeated stimulation, seizure duration lengthens and behavior intensifies until these characteristics reach a plateau. 3Among different brain regions the piriform cortex and hippocampus are recognized as two important structures involved in the development and control of kindled seizures. 4,5 These two structures are interconnected by reciprocal ABSTRACT: Introduction: The hippocampus and piriform cortex have a critical role in seizure propagation. In this study, the role of adenosine A 1 receptors of piriform cortex on CA1 hippocampal kindled seizures was studied in rats. Methods: Animals were implanted with a tripolar electrode in the right hippocampal CA1 region and two guide cannulae in the left and right piriform cortex. They were kindled by daily electrical stimulation of hippocampus. In fully kindled rats, N 6 -cyclohexyladenosine (CHA; a selective adenosine A 1 receptors agonist) and 1,3-dimethyl-8-cyclopenthylxanthine (CPT a selective adenosine A 1 receptor antagonist) were microinfused into the piriform cortex. The animals were stimulated at 5, 15 and 90 minutes (min) after drug injection. Results: Obtained data showed that CHA (10 and 100 µM) reduced afterdischarge duration, stage 5 seizure duration, and total seizure duration at 5 and 15 min after drug injection. There was no significant change in latency to stage 4 seizure. CPT at concentration of 20 µM increased afterdischarge duration, stage 5 seizure duration, and total seizure duration and decreased latency to stage 4 seizure at 5 and 15 min post injection. Pretreatment of rats with CPT (10 µM), 5 min before CHA (100 µM), reduced the effect of CHA on seizure parameters. Conclusion: These results suggested that activity of adenosine A 1 receptors in the piriform cortex has an anticonvulsant effect on kindled seizures resulting from electrical stimulation of the CA 1 region of the hippocampus.RÉSUMÉ: Le rôle des récepteurs A1 de l'adénosine du cortex piriforme dans l'embrasement de l'hippocampe. Contexte : L'hippocampe et le cortex piriforme jouent un rôle déterminant dans la propagation des crises d'épilepsie. Dans cette étude, nous avons évalué le rôle des récepteurs A1 de l'adénosine du cortex piriforme sur les crises provoquées par embrasement de la région CA1 de l'hippocampe chez des rats. Méthodes : Nous avons implanté une électrode tripolaire dans la région CA1 droite de l'hippocampe des rats et deux canules guides, dans le cortex piriforme gauche et droit. L'hippocampe était ensuite stimulé électriquement à tous les jours. Chez les ra...

G-protein coupled receptors may have a role in mediating the antiepileptogenic effect of low-frequency stimulation (LFS) on kindling acquisition. This effect is accompanied by changes at the intracellular level of cAMP. In the present study, the effect of rolipram as a phosphodiesterase inhibitor on the antiepileptogenic effect of LFS was investigated. Meanwhile, the expression of α- and α-subunit of G proteins and regulators of G-protein signaling (RGS) proteins following LFS application was measured. Male Wistar rats were kindled by perforant path stimulation in a semi-rapid kindling manner (12 stimulations per day) during a period of 6days. Application of LFS (0.1ms pulse duration at 1Hz, 200 pulses, 50-150μA, 5min after termination of daily kindling stimulations) to the perforant path retarded the kindling development and prevented the kindling-induced potentiation and kindling-induced changes in paired pulse indices in the dentate gyrus. Intra-cerebroventricular microinjection of rolipram (0.25μM) partially prevented these LFS effects. Twenty-four hours after the last kindling stimulation, the dentate gyrus was removed and changes in protein expression were measured by Western blotting. There was no significant difference in the expression of α-subunit of G and G proteins in different experimental groups. However, application of LFS during the kindling procedure decreased the expression RGS4 and RGS10 proteins (that reduce the activity of G) and prevented the kindling-induced decrease of RGS2 protein (which reduces the G activity). Therefore, it can be postulated that the G protein signaling pathways may be involved in antiepileptogenetic effect of LFS, and this is why decreasing the cAMP metabolism by rolipram attenuates this effect of LFS.