Anticonvulsant action and long-term effects of gabapentin in the immature brain

The anticonvulsant action and the long-term effects on learning, memory and behavior of the new generation antiepileptic drug gabapentin (GBP) were in vestigated in immature animals. Kainic acid (KA) was administered to rats o n postnatal day (P) 35. Animals were treated with GBP or saline from P36 to P75 and spontaneous seizure frequency was monitored. After tapering the dr ug, the rats were tested in the water maze and open field test. Brains were then analyzed for histological lesions. Animals treated with GBP following KA-induced status epilepticus had a reduced incidence of spontaneous recur rent seizures, a better pathology score, and less aggressiveness compared t o saline-treated controls. Effectiveness of GBP on seizure threshold was te sted using flurothyl inhalation in 10 separate age groups of animals rangin g from the newborn period to adulthood. Furthermore, GBP plasma concentrati on peaks were determined in all age groups. At all ages, GBP pre-treated an imals demonstrated a higher seizure threshold. Plasma GBP concentrations di d not significantly change with age. These data suggest that acute administ ration of a single therapeutic dose of GBP increases the seizure threshold at all ages studied, while chronic treatment following the status reduces s pontaneous seizure frequency and cell damage and has no long-term adverse c onsequences on cognitive processes during development. (C) 2000 Elsevier Sc ience Ltd. All rights reserved.