ACETAZOLAMIDE WITH CAFFEINE CAUSES EXENCEPHALY IN RESISTANT SWV MICE

Pregnant SWV mice were treated on day 9 of gestation (PC) with 50 mg/k g of caffeine (CAFF), 200 mg/kg (LD) or 1000 mg/kg (HD) of acetazolami de (ACZM), or a combination of both agents, or on day 8 PC with both a gents (ACZM + CAFF). Untreated (UNTD) and vehicle-treated (VEH) groups served as controls. The SWV strain is widely reported to be resistant to ACZM; it was resistant to ACZM or CAFF + ACZM when treated on day 9 of gestation, but a significant frequency of malformations, primaril y exencephaly, was produced by ACZM + CAFF on day 8 PC. This study pro vides evidence that ACZM, coupled with a subteratogenic dose of caffei ne can produce abnormalities in the ''resistant'' SWV mice, using the endpoint of exencephaly on day 8 of gestation. The mean number of ossi fied caudal vertebrae in day-9 treatments and ossified cervical verteb ral centra in day-8 treatments were reduced. The frequency of ossifica tion of the first cervical vertebra (C1) was reduced from 93% in UNTD to 39% in HD-ACZM day 9 PC and 69% in HD-ACZM + CAFF day 9 PC groups, and was also significantly reduced in the HD-ACZM + CAFF day-8 treated group.