Abstract:
: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.
journal_name
Neurotoxicol Teratoljournal_title
Neurotoxicology and teratologyauthors
Wolansky MJ,Azcurra JMdoi
10.1016/j.ntt.2004.12.006subject
Has Abstractpub_date
2005-03-01 00:00:00pages
299-310issue
2eissn
0892-0362issn
1872-9738pii
S0892-0362(05)00002-4journal_volume
27pub_type
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