Comparison of the Effects of Adenosine A1 Receptors Activity in CA1 Region of the Hippocampus on Entorhinal Cortex and Amygdala Kindled Seizures in Rats

Introduction & In the CNS, adenosine is known to suppress repetitive neuronal Firing, suggesting a role as an endogenous modifier of seizures. Indeed, intracerebral adenosine concentrations rise acutely during seizure activity and are thought to be responsible for terminating seizures and establishing a period of post-ictal refractoriness. However, it is unclear whether this suppression results from a general depression of brain excitability or through action on particular sites critical for the control of after discharge generation and/or seizure development and propagation. In this regard, comparison of the effects of adenosine A1 receptors of CA1 (region of the ‎hippocampus) on entorhinal cortex and amygdala kindled seizures was ‎investigated in this study. In this experimental study, Animals were kindled by daily electrical stimulation of amygdale (group A) or entorhinal cortex (group B). In the fully kindled animals, N6-‎cyclohexyladenosine (CHA;1 and 10 mM; a selective adenosine A1 receptor ‎agonist) and 1,3-dimethyl-8-cyclohexylxanthine(CPT;1 ‎µ‎M; a selective ‎adenosine A1 receptors antagonist) were microinfused bilaterally into the CA1 ‎region of hippocampus (1ml/2min) and animals were stimulated at 5 and 15 minutes after drug ‎injection. All animals were received artificial cerebrospinal fluid, 24 h before ‎each drug injection and this result were used as control. The seizure parameters were measured at 5 and 15min post injection. Obtained data showed that CHA at concentrations of 10 ‎µ‎M reduced ‎entorhinal cortex and amygdala after discharge and stage5 seizure durations and ‎increased stage4 latency. CHA at concentration 1‎µ‎M significantly alters ‎seizure parameters of group A but not effect on group B. Intrahippocampal (CA1 region) pretreatment of CPT (1 ‎µ‎M) before CHA abolished the effects of CHA on seizure parameters. It ‎may be suggested that hippocampal CA1 region plays an important role in ‎seizure propagation from entorhinal cortex and amygdala to other brain ‎region/s and activation of adenosine A1 receptors in this region have ‎anticonvulsant effects on amygdala rather than entorhinal cortex kindled ‎seizures.