Different effects of postnatal caffeine treatment on two pentylenetetrazole-induced seizure models persist into adulthood Jana D. Tchekalarova, Hana Kubová, Pavel Mareš CZ-142 20, Academy of Sciences of Czech Republic, Institute of Physiology, Vide ská 1083, Prague 4, Czech Republic Correspondence: Jana D. Tchekalarova, e-mail: janetchekalarova@gmail.com Abstract: Background: Postnatal treatment with caffeine from P7 to P11 (10 or 20 mg/kg daily) resulted in transient changes in two pentyle- netetrazole (PTZ)-induced models of epileptic seizures characterized by spike-and-wave EEG rhythm in immature rats. To know if some changes persist into adulthood we studied these models in young adult Wistar rats. Methods: Caffeine treatment at a daily dose of 10 and/or 20 mg/kg, sc was executed during postnatal days 7–11. Rhythmic metrazol activity (RMA, model of human absences) was induced in 60-day old rats by two successive doses of PTZ (20 + 20 mg/kg, ip) while for induction of minimal clonic seizures (model of human myoclonic seizures) the second dose of PTZ was 40 mg/kg. Results: RMA episodes elicited by the 20 + 20 mg/kg dose of PTZ in adult rats exposed to caffeine at P7 to P11 were decreased. This effect was more pronounced in group treated with the higher dose of caffeine. In contrast, the lower dose of caffeine exacerbated minimal clonic seizures (both incidence and intensity were increased). In addition, some animals from the 20-mg/kg caffeine group exhibited transition to generalized tonic-clonic seizures. Conclusion: Different effects of postnatal caffeine exposure persist into adulthood; the seizure ameliorating effects in a model of ab- sences and seizure exacerbating action in a model of myoclonic seizures are dose-specific. Key words: caffeine, postnatal treatment, pentylenetetrazole, spike-and-wave episodes, minimal clonic seizures, rats Introduction Caffeine represents one of the most extensively self- administered substance in the world. Caffeine and various analogs, are prescribed as analgesics, stimu- lant adjuvants, antiinflammatories, antitussives, diu- retics/natriuretics, and lipolytics [4]. Moreover, me- thylxanthines are routinely used in neonatal medicine either acutely or chronically for suppression of apneic episodes in premature infants [3, 28]. Both clinical and experimental evidence on safety and long-term consequences of chronic caffeine administration are scarce [28, 32]. Recent report demonstrated that caf- feine improved the rate of survival without neurode- velopmental disability at a corrected age of 18 to 21 months [33]. However, the long-term drug-induced blockade of adenosine receptors at early stages of maturation may modify brain development and have late consequences on brain excitability. There is evi- dence that neonatal caffeine treatment alters adeno- sinergic neuromodulation of the respiratory control 847