Wolansky Marcelo Javier, Azcurra Julio Marcos
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.
Neurotoxicol Teratol. 2005 Mar-Apr;27(2):299-310. doi: 10.1016/j.ntt.2004.12.006.
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.
实验模型和临床数据表明，孕期服用苯妥英钠（PHT）的癫痫母亲所生子女出现运动和学习障碍的发生率可能会增加。关于婴儿在孕期或生命早期接触PHT（即婴儿惊厥治疗）后对PHT诱导的长期行为毒性的易感性，相关数据很少。我们研究了孕期、婴儿期或两者都接触PHT所诱导的转圈行为改变的持续性。在妊娠第10 - 18天，对怀孕的斯普拉格-道利大鼠腹腔注射生理盐水（SAL）或PHT（30毫克/千克/天）。然后在出生后第13 - 23天，对后代腹腔注射SAL或PHT（60毫克/千克/天）。之后，在三个时间点进行转圈训练测试。在出生后第40天和第80天，强化顺时针方向的转圈。在出生后第150天，改为奖励逆时针方向的转圈。在出生后第40天，与生理盐水处理的对照组相比，所有PHT处理组的转圈速度都有所增加。在仅孕期暴露和仅婴儿期暴露组中，也观察到更高的转圈方向空间错误率。在出生后第80天，孕期暴露组的转圈速度高于对照组或仅婴儿期暴露组。在出生后第150天，孕期暴露组在反向学习任务中的转圈速度明显增加。这些结果表明，出生后早期接触PHT可能会加剧孕期接触已知的长期行为影响。
