Biologia, Bratislava, 55/Suppl. 8: 125-130, 2001.
ISSN 0006-3088 (Biologia). ISSN 1335-6399 (Biologia. Section Cellular and Molecular Biology).
Effect of phenytoin on prenatal and postnatal development of rats.
Eduard Ujhazy1*, Michal Dubovicky1, Mojmir Mach1, Ivo Juranek1, Jana Navarova1, Irina Sadlonova2 & Andrej Gajdosik1
1 Institute of Experimental Pharmacology, Slovak Academy of Sciences, Dubravska cesta 9, SK-84216 Bratislava, Slovakia; tel.: ++ 421 7 59410664, e-mail: email@example.com
2 Drug Research Institute, J.S.C., Horna 36, SK-90001 Modra, Slovakia
* corresponding author
Received: July 24, 2000 / Accepted: October 24, 2000
Wistar/DV rats were treated with phenytoin (PHT, 150 mg/kg) orally from day 2 to 19 of gestation. On day 20 of gestation teratological examination was performed. The physical and behavioural development of the offspring of the remaining part of pregnant rats was observed from birth up to 100 days of age. PHT administration caused decreased maternal weight during the late period of gestation and high mortality of offspring (84%) occurred prior to the 4th day of age. Teratological investigation revealed a significant decrease of foetal and placental weight and increased incidence of skeletal anomalies. As for neurobehavioural development of offspring, an acceleration in the righting reflex on postnatal day (PD) 5 and decrease in the intensity of rearing in an open field on PD 100 was observed. In adulthood, the PHT-influenced offspring showed a typical behavioural abnormality - circling behaviour. The study confirmed that prenatal administration of PHT resulted in morphological and neurobehavioural changes in Wistar/DV rats.
Key words: phenytoin, teratogenicity, intrauterine hypoxia, behaviour, offspring, rat.