%0 Journal Article
%T Prenatal Exposure to Lamotrigine: Effects on Postnatal Development and Behaviour in Rat Offspring
%A Sekar Sathiya
%A Murugan Ganesh
%A Periyathambi Kalaivani
%A Vijayan Ranju
%A Srinivasan Janani
%A Bakthavachalam Pramila
%A Chidambaram Saravana Babu
%J ISRN Neuroscience
%D 2014
%R 10.1155/2014/163459
%X 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¨C180£¿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. 1. Introduction Use of antiepileptic drugs (AEDs) during pregnancy presents the dilemma of minimising the risk of seizure and avoiding adverse effects in the unborn child. Various studies revealed that prenatal exposure of AEDs imparts serious effects on infants [1¨C3]. Further, prenatal exposures to AEDs were also reported to produce cognitive impairment [4, 5]. Vigabatrin and valproate were reported to produce neuronal migration defect [6] upon prenatal exposure. Janz and Fuchs [7] reviewed that exposure to AED during pregnancy increases the risk of miscarriage and stillbirth rate. However, little attention was paid to the cellular effects of AEDs during postnatal development and in adulthood. Lamotrigine (LTG), a phenyltriazine derivative, is one of the most widely used second-generation antiepileptic agents used for both partial and generalised seizures. In pregnant women, LTG is reported to produce side effects such as rash, mania, memory and cognitive problems, mood changes, runny nose, cough, nausea, indigestion, abdominal pain, weight loss, vaginitis, and leukopenia and retardation in development of fetus [8¨C10]. Recently, exposure to LTG during pregnancy was shown to impart adverse outcome within different developmental domains [11]. On the other hand its use in pregnancy is associated with risk of
%U http://www.hindawi.com/journals/isrn.neuroscience/2014/163459/