Different effects of postnatal caffeine treatment on two pentylenetetrazole-induced seizure models persist into adulthood

Pharmacol Rep. 2013;65(4):847-53. doi: 10.1016/s1734-1140(13)71065-x.

Abstract

Background: Postnatal treatment with caffeine from P7 to P11 (10 or 20 mg/kg daily) resulted in transient changes in two pentylenetetrazole (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 absences and seizure exacerbating action in a model of myoclonic seizures are dose-specific.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging* / drug effects
  • Animals
  • Caffeine / administration & dosage
  • Caffeine / therapeutic use*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Epilepsies, Myoclonic / chemically induced
  • Epilepsies, Myoclonic / drug therapy*
  • Epilepsy, Absence / chemically induced
  • Epilepsy, Absence / drug therapy*
  • Male
  • Pentylenetetrazole*
  • Rats

Substances

  • Caffeine
  • Pentylenetetrazole