Anticonvulsant action of allopregnanolone in immature rats.

Abstract

Anticonvulsant activity of allopregnanolone, a neurosteroid allosterically modulating GABA(A) receptor was tested in a model of motor seizures elicited by pentetrazol in immature rats. Rats 7, 12, 18, 25 or 90 days old were pretreated with allopregnanolone in doses from 5 to 40 mg/kg i.p. and 15 min later pentetrazol was injected subcutaneously in a dose of 100 mg/kg. Rats were observed in isolation for 30 min. Allopregnanolone dose-dependently suppressed both generalized tonic-clonic and minimal clonic seizures with the highest efficacy in 12-day-old rats. Anticonvulsant action was least expressed in adult animals. Duration of anticonvulsant action tested after a dose of 20 mg/kg in 12- and 90-day-old rats demonstrated markedly longer effects in young rats. Allopregnanolone compromised motor performance of rats but duration of this unwanted effect in 12-day-old rats was shorter than duration of anticonvulsant action. This difference can be important for possible clinical use of neurosteroids.