Abstracts

Rationale: Recently we demonstrated that nonspecific adenosine receptor agonist 2-chloroadenosine exhibits marked anticonvulsant action against cortical epileptic afterdischarges (ADs) in immature rats. We decided to differentiate a role of two types of adenosine receptors present in the brain (A1 and A2A) in this action. Methods: Rats 12, 18 and 25 days old with implanted epidural stimulation and recording electrodes were studied. Fifteen-second stimulation series consisted from 1-ms biphasic pulses delivered at 8-Hz frequency. These stimulation series were repeated six times with 10-min intervals, intensity was just suprathreshold for elicitation of ADs. Drugs were injected 5 min after the first AD. Agonists of A1 (CCPA) and A2A receptors (CGS21680) as well as antagonists (DCPCX for A1 and ZM241385 for A2A receptors) were administered in two different doses according to our data from experiments with pentetrazol-induced seizures. Control animals received either saline (control for CCPA) or dimethylsulfoxide (controls for the three other drugs). Duration of the ADs was measured and motor phenomena (movements during stimulation and clonic seizures accompanying ADs) were quantified. Results: Repeated stimulation resulted in progressive prolongation of ADs in control rats, especially in 12-day-old ones. Duration of ADs was extremely (up to 17fold) prolonged by A1 receptor antagonist DPCPX, and shortened by an agonist CCPA. This effect was more marked in 12-day-old rats and moderate (effect of the antagonist) or nearly negligible (effect of the agonist) in 25-day-old ones. Drugs affecting A2A adenosine receptors did not significantly influence duration of ADs, only a tendency to suppression of progressive prolongation was observed with both agonist CGS21680 and antagonist ZM241385 in 12-day-old animals. None drug influenced movements induced directly by stimulation as well as clonic seizures forming a motor counterpart of ADs. Conclusions: Adenosine action on A1 receptors is the mechanism of its anticonvulsant action in a model of cortical seizures. The role of these receptors is more important at early than at later developmental stages what indicates that agonists of A1 adenosine receptors may be a source of anticonvulsants specific for infant and early childhood epilepsies. This study was supported by a grant No.NR/9184-3 of the Grant Agency of Ministry of Health and a grant No.P304/10/1274 of the Grant Agency of the Czech Republic.