Sathiya Sekar, Ganesh Murugan, Kalaivani Periyathambi, Ranju Vijayan, Janani Srinivasan, Pramila Bakthavachalam, Saravana Babu Chidambaram
Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai, Tamil Nadu 600116, India.
Department of Biochemistry, Sri Ramachandra University, Chennai, Tamil Nadu 600116, India.
ISRN Neurosci. 2014 Apr 14;2014:163459. doi: 10.1155/2014/163459. eCollection 2014.
Use of antiepileptic drugs (AEDs) in pregnancy warrants various side effects and also deleterious effects on fetal development. The present study was carried out to assess the effects of prenatal exposure to lamotrigine (LTG) on postnatal development and behavioural alterations of offspring. Adult male and female Sprague Dawley rats weighing 150-180 g b. wt. were allowed to copulate and pregnancy was confirmed by vaginal cytology. Pregnant rats were treated with LTG (11.5, 23, and 46 mg/kg, p.o) from gestational day 3 (GND 3) and this treatment continued till postnatal day 11 (PND 11). Offspring were separated from their dam on day 21 following parturition. LTG, at 46 mg/kg, p.o, produced severe clinical signs of toxicity leading to death of dam between GND 15 and 17. LTG, at 11.5 and 23 mg/kg, p.o, showed significant alterations in offspring's incisors eruption and vaginal opening when compared to age matched controls. LTG (23 mg/kg, p.o) exposed female offspring expressed hyperactive behaviour and decreased GABA-A receptor expression when compared to control rats. These results reveal that prenatal exposure to LTG may impart differential postnatal behavioural alterations between male and female rats which paves way for further investigations.
孕期使用抗癫痫药物（AEDs）会产生各种副作用，对胎儿发育也有有害影响。本研究旨在评估产前暴露于拉莫三嗪（LTG）对后代产后发育和行为改变的影响。选取体重150 - 180 g体重的成年雄性和雌性Sprague Dawley大鼠进行交配，通过阴道细胞学检查确认怀孕。怀孕大鼠从妊娠第3天（GND 3）开始接受LTG（11.5、23和46 mg/kg，口服）治疗，该治疗持续至出生后第11天（PND 11）。产后第21天，将后代与母鼠分开。口服46 mg/kg的LTG产生了严重的毒性临床症状，导致母鼠在GND 15至17之间死亡。与年龄匹配的对照组相比，口服11.5和23 mg/kg的LTG显示后代的门齿萌出和阴道开口有显著改变。与对照大鼠相比，暴露于LTG（23 mg/kg，口服）的雌性后代表现出多动行为，且GABA - A受体表达降低。这些结果表明，产前暴露于LTG可能会使雄性和雌性大鼠在产后产生不同的行为改变，这为进一步研究铺平了道路。
