Convulsant action of systemically administered glutamate and bicuculline methiodide in immature rats

Developmental changes of transport of drugs into the brain play an importan t role in ontogenetic neuropharmacology. Two convulsant drugs with differen t mechanisms of action (glutamate and bicuculline methiodide) were chosen t o demonstrate these changes in developing rats. High dose of glutamate (4 g /kg i.p.) induced both minimal (predominantly clonic) and generalized tonic -clonic seizures in rat pups 7, 12, and 18 days old. In contrast, seizures were only exceptionally observed in 25 and 90 days old animals. Bicuculline methiodide was administered in a dose of 2 or 20 mg/kg i.p. The first sign of bicuculline methiodide action in all age groups was represented by auto matisms, a symptomatology never seen after bicuculline hydrochloride admini stration. Minimal seizures were induced in 12-day-old and in a few 18-day-o ld and adult rats. Generalized seizures were common after the higher dose o f bicuculline methiodide in 7- and 12-day-old rat pups, seldom in 18-day-ol d ones and never seen in 25-day-old and adult animals. Both glutamate and b icuculline methiodide enter the brain in immature rats but the mechanisms a re probably different - glutamate is transported actively through the blood -brain barrier whereas no similar system is known for bicuculline methiodid e. (C) 2000 Elsevier Science B.V. All rights reserved.