Prenatal methotrexate exposure decreases seizure susceptibility in young rats of two strains

Effects of prenatal exposure to methotrexate (MTX) administered in Sprague- Dawley (one 5 mg/kg dose of MTX on gestational day 15; E15) or Wistar (one 5 mg/kg dose of MTX on E14 or E15 or two such doses on E15) pregnant rat da ms were studied in developing offspring. Young Sprague-Dawley rats were sub jected to rapid kindling on postnatal days (PN) 15 and 16, and to flurothyl seizures on PN 15 and PN 30, Offspring of the Wistar strain were tested in flurothyl on PN 30, In Sprague-Dawley rats, prenatal exposure to MTX decre ased susceptibility to kindling-induced seizures on PN 15 and to flurothyl- induced clonic seizures on PN 30, In Wistar rats, a single dose of MTX on E 15 was ineffective, but two doses significantly decreased susceptibility to flurothyl-induced seizures. Additionally, due to a shorter duration of pre gnancy in Wistar rats, exposure to a single dose of MTX on E14 also decreas ed susceptibility to flurothyl seizures. MTX, as folic acid antagonist, int erferes with DNA synthesis, However, unlike other treatments that suppress DNA synthesis (such as methylazoxymethanol exposure or X-ray radiation), MT X exposure results in anticonvulsant effects in surviving offspring. The da ta suggest that not all prenatal impairments of DNA have proconvulsant feat ures postnatally, (C) 2000 Academic Press.