Postnatal period of caffeine treatment and time of testing modulate the effect of acute caffeine on cortical epileptic afterdischarges in rats

Recently, we have found that postnatal caffeine treatment results in a dose-dependent pro- or anticonvulsant effect during brain maturation which effect is transient and disappears in adult rats. The aim of the present study was to determine whether the developmental period of chronic caffeine treatment and the age of testing are crucial for the effects of acute caffeine on cortical epileptic afterdischarges (ADs) in rats. Rhythmic electrical stimulation of somatosensory cortex was applied to elicit EEG and motor phenomena in 18- and 25-day-old rats, respectively. Acute injection of caffeine (10 and 20 mg/kg s.c.) decreased the threshold for stimulation-bound movements in both age groups while it increased the thresholds for spike-and-wave ADs and clonic seizures accompanying them at P25. Acute caffeine had a similar effect on thresholds for spike-and-wave ADs and clonic seizures in 25-day-old rats exposed to the methylxanthine at P7–P11 and P13–17, respectively. Though caffeine administration per se did not change the duration of ADs at P18 it produced either a pro- or anticonvulsant effect after postnatal treatment (P7–P11 and P13–P17, respectively). However, acute caffeine exerted a prolongation of ADs at P25 which effect was alleviated after both developmental periods of treatment. Taken together, acute caffeine effects on cortical epileptic ADs in rats can be modulated by the postnatal period of treatment and age of testing.

Research highlights
► Caffeine administration per se did not change the duration of afterdischarges (ADs) at P18;
► Acute caffeine i) decreased the threshold for stimulation-bound movements, ii) increased thresholds for spike-and-wave ADs and clonic seizures accompanying them and iii) exerted a prolongation of ADs at P25;
► Re-challenge with caffeine at P18 had a moderate proconvulsant effect in rats exposed to the methylxanthine during the early postnatal period (P7–P11).
► In contrast, re-challenge with caffeine exhibited an anticonvulsant action in both 18- (increased thresholds for elicitation of spike-and-wave afterdischarges) and 25-day-old rats (attenuated the prolongation of afterdischarges) exposed to the same drug at P13–P17.
► Both developmental period of caffeine treatment and stage when acute caffeine effect is tested are of primary importance for delayed consequences on seizure susceptibility in immature rats.