Convulsive thresholds and severity and the anticonvulsant effect of phenobarbital and phenytoin in adult rats administered 6-hydroxydopamine or 5,7-dihydroxytryptamine during postnatal development.

Rats were administered intracisternal 6-hydroxydopamine (6-OHDA) or 5,7-dihydroxytryptamine (5,7-DHT) within the first three postnatal days, at several ages centered on the third postnatal week or on postnatal day 180. When the rats were 210-days-old, maximal electroshock convulsive thresholds and responses and the anticonvulsant effect of phenobarbital and phenytoin were determined. All 5,7-DHT treatments resulted in an approximate 21% decrease in the tonic convulsive threshold and increased the incidence of tonic hindlimb extension (HLE). Only the 5,7-DHT treatment at 180 days was associated with a more severe HLE response (shortened onset and prolonged duration). All neonatal 6-OHDA treatments were associated with no change in the tonic threshold, but increased the incidence and severity of HLE. The latter effect depended on the postnatal age of 6-OHDA-treatment: treatment at postnatal days 14 and 15 resulted in the greatest increase in severity (52% decrease in onset and 48% increase in duration). The 6-OHDA treatment to 180-day-old rats increased the incidence and duration of HLE but had no influence on the tonic threshold or onset of extension. The effectiveness of both phenobarbital and phenytoin to block HLE was variably decreased by all neurotoxin treatments. The results suggest that interference with the postnatal maturation of monoaminergic influences on seizure processes can have a long-lasting influence on the ability of the brain to limit the generation and spread of seizure activity and on the effectiveness of anticonvulsant drugs.