Biphasic effect of chronic postnatal caffeine treatment on cortical epileptic afterdischarges during ontogeny in rats

EEG and motor phenomena elicited by stimulation of sensorimotor cortex were used to study the effects of chronic postnatal administration of caffeine (10 and 20 mg/kg, s.c. from P7 to P11) in rats. Rhythmic electrical stimulation was applied to 12-, 18-, 25- and 67-day-old rats with implanted electrodes. Animals with the higher dose of caffeine exhibited increased thresholds for elicitation of stimulation-bound movements, spike-and-wave afterdischarges (ADs) and clonic seizures accompanying these ADs at the age of 12 days and decreased duration of spike-and-wave ADs at postnatal days (P) 18 and 25. In contrast, chronic administration of the lower dose of caffeine resulted in a proconvulsant effect expressed as a significant prolongation of spike-and-wave ADs in P12, P18 and P25 groups as well as of the second "limbic" type of ADs (significant only in P12 and P25). The biphasic action of chronic postnatal caffeine treatment was transient and was no longer present in 67-day-old rats. Our results demonstrate that early postnatal caffeine exposure results in either pro- or anticonvulsant effect during brain maturation in relation to the dose used. Caffeine is a mixed adenosine receptor antagonist, therefore its effects could be due to a different action on adenosine receptor subtypes; an additional mechanism of action cannot be excluded.