Permanent motor activity and learning disorders induced by exposure to phenytoin during gestation and early infancy in the rat.
Experimental models and clinical data indicate that the incidence of motor and learning disorders may be increased in children of epileptic mothers taking phenytoin (PHT) during pregnancy. There is little data on the vulnerability of infants to PHT-induced long-term behavioral toxicity after gestational or early life exposure (i.e., infantile convulsion therapy). We examined the persistence of alterations in circling behavior induced by exposure to PHT during gestation, infancy, or both. Pregnant Sprague-Dawley rats were injected i.p. with saline (SAL) or PHT (30 mg/kg/day) during gestational days (GD) 10-18. The offspring were then administered (i.p.) SAL or PHT (60 mg/kg/day) during postnatal days (PD) 13-23. Afterward, Circling Training tests were performed at three time points. At PD40 and PD80, the clockwise direction of circling was reinforced. At PD150, counterclockwise circling was rewarded instead. At PD40, all PHT-treated groups demonstrated increased circling velocities compared to saline-treated controls. Higher spatial error rates for direction of circling were also observed in gestation-only and infancy-only exposures. At PD80, groups exposed during gestation had higher circling velocities than control or infancy-only exposed groups. At PD150, increases in circling velocity were apparent for the reverse learning task in groups exposed during gestation. These results indicate that early postnatal exposure to PHT may exacerbate the known long-term behavioral effects of gestational exposure.
Wolansky
Marcelo Javier
MJ
Interdisciplinary Project on Neuroteratology, Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Ciudad Universitaria, Universidad de Buenos Aires, Buenos Aires, Argentina. wolansky.marcelo@epa.gov
Azcurra
Julio Marcos
JM
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D001724:Birth Weight / Q000187:drug effects; D005260:Female; D007859:Learning Disabilities / Q000139:chemically induced*; D008098:Litter Size / Q000187:drug effects; D008425:Maternal Behavior / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D010672:Phenytoin / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012193:Reversal Learning / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects; D016019:Survival Analysis
D000927:Anticonvulsants; D010672:Phenytoin