Abstracts

Rationale: Adenosine is presumed to be an endogenous anticonvulsant in the brain. A1 receptors responsible for its anticonvulsant action were demonstrated in adult as well as immature rats; an agonist of these receptors CCPA (6-chloro-cyclopentyladenosine) was used to study possible changes in the anticonvulsant action of adenosinergic system after status epilepticus (SE) induced in immature rats. Cortical epileptic afterdischarges (CxADs) were used as a model of epileptic seizures. Methods: Lithium-pilocarpine status epilepticus was elicited in rats 12 days old (P12). Cortical epileptic afterdischarges were elicited by 15-s series of 8-Hz stimulation of sensorimotor cortex in rats 3, 6, 9 and 13 days after SE (i.e.at P15, P18, P21 and P25). Intensity of stimulation current was increased stepwise from 0.8 to 15.0 mA, intervals between individual stimulation series were 10 min. Immediately after the 3.5-mA stimulation, CCPA was administered at doses of 0.5 or 1 mg/kg i.p. Control siblings were handled in the same way as SE rats, only pilocarpine was replaced by saline. Thresholds for individual phenomena (movements directly bound to stimuli, spike-and-wave ADs, clonic seizures, transition into limbic type of ADs characterized by epileptic automatisms, described as mixed ADs) and duration of CxADs were measured and statistically evaluated. In addition to total duration of ADs duration of spike-and-wave as well as of mixed ADs were measured. Statistical evaluation was performed using SigmaStat program®, level of significance was put at 5%. Results: Threshold intensities for elicitation of movements directly evoked by stimulation, spike-and-wave ADs and clonic seizures accompanying this type of ADs were higher in SE than control 15-day-old rats but not in older animals. Thresholds for transition into limbic type of ADs decreased with age - from P15 in control rats and from P18 in SE rats.Progressive prolongation of ADs with increasing stimulation intensity was interrupted by CCPA in the three younger groups, duration started to increase again after 30 min (i.e.after the 7.5-mA stimulation). This increase appeared earlier and was steeper in control than in SE rats. The significant differences were maintained after the high intensities (9 mA and more) and were best expressed in P15 rats. There was no marked change in P25 rats. Nearly the same changes were seen if S-and-W ADs were evaluated. Mixed ADs were significantly shortened in P15 rats only. Conclusions: An agonist of A1 adenosine receptors CCPA exhibits an anticonvulsant action even in immature rats after status epilepticus. Its action was marked 3 and 6 days after status and decreased in P18 rats. Effect in SE rats was stronger than in control animals. CCPA did not exhibit any anticonvulsant action in P25 animals (i.e.13 days after SE). Funding: This study was supported by grants of the Czech Grant Agency Nos.15-16605S and 16-04726S.