Effects of postnatal caffeine exposure on seizure susceptibility in developing rats

Postnatal caffeine treatment of rats can influence brain excitability during development. To study the mechanism involved in the alterations of seizure susceptibility, we used an animal model that corresponds to the infants treated with caffeine for apnea of prematurity. Seizure susceptibility to four convulsant drugs (pentetrazol, picrotoxin, bicuculline and aminophylline) was assessed in 12- and 25-day-old rats exposed to caffeine at a daily dose of 10 and/or 20 mg/kg s.c. at postnatal days 7–11. Our results demonstrated that the changes in generalized tonic–clonic seizures (GTCS) are more expressed than changes in minimal clonic seizures. There are marked differences among individual convulsants with the highest sensitivity of aminophylline-induced seizures and nearly complete resistance of bicuculline-induced seizures. The changes in individual models are age specific: aminophylline- and picrotoxin-induced seizures are more affected in 12- than in 25-day-old rats whereas PTZ-induced seizures are more changed by early postnatal caffeine exposure in 25- than in 12-day-old animal. Taken together, repeated caffeine treatment from postnatal day 7 to 11 reduces the seizure susceptibility during development and this reduction is also model specific.