ANTICONVULSANT DOSES OF CARBAMAZEPINE INCREASE HIPPOCAMPAL EXTRACELLULAR SEROTONIN IN GENETICALLY EPILEPSY-PRONE RATS - DOSE-RESPONSE RELATIONSHIPS

The antiepileptic drug carbamazepine produces dose related anticonvuls ant effects in genetically epilepsy-prone rats (GEPRs) and most other animal seizure models. Carbamazepine releases serotonin as part of the pharmacodynamic action by which it suppresses convulsions in GEPRs an d it releases serotonin in non-epileptic Sprague-Dawley rats. The two strains which make up the GEPR seizure model (moderate seizure GEPR-3s and severe seizure GEPR-9s) experience anticonvulsant effects in resp onse to different doses of carbamazepine (GEPR-3 ED50=25 mg/kg; GEPR-9 ED50=3 mg/kg). The present study determined that carbamazepine produc es a dose related increase in extracellular serotonin in each of the t wo GEPR strains. The doses of carbamazepine required to increase extra cellular serotonin are similar to the doses required for an anticonvul sant effect in each of the strains. This result provides further suppo rt for the hypothesis that release of serotonin by carbamazepine is an important part of the pharmacodynamic action by which this drug suppr esses seizures. (C) 1997 Elsevier Science Ireland Ltd.