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Published on: November 20, 2015
Prenatal exposure to lamotrigine: effects on postnatal development and behaviour in rat offspring
Sekar Sathiya1, Murugan Ganesh2, Periyathambi Kalaivani1
1Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai, Tamil Nadu 600116, India.
Insights
Prenatal exposure to lamotrigine (LTG) in rats can cause developmental issues and behavioral changes in offspring. Female offspring exposed to LTG showed hyperactivity and reduced GABA-A receptor expression.
Area of Science:
- Neuroscience
- Developmental Toxicology
- Pharmacology
Background:
- Antiepileptic drugs (AEDs) use during pregnancy poses risks to fetal development.
- Lamotrigine (LTG) is an antiepileptic drug with potential developmental effects.
- Understanding LTG's impact on offspring is crucial for managing epilepsy in pregnant individuals.
Purpose of the Study:
- To investigate the effects of prenatal lamotrigine (LTG) exposure on postnatal development and behavior in Sprague Dawley rats.
- To assess dose-dependent toxicity and developmental alterations in offspring following maternal LTG treatment.
- To explore potential sex-specific behavioral changes and neurochemical alterations in offspring.
Main Methods:
- Pregnant Sprague Dawley rats were administered LTG (11.5, 23, 46 mg/kg) from gestational day 3 to postnatal day 11.
- Offspring development was monitored through parameters like incisor eruption and vaginal opening.
- Behavioral assessments and GABA-A receptor expression analysis were conducted on offspring.
Main Results:
- Maternal LTG administration at 46 mg/kg resulted in significant toxicity and mortality.
- Lower LTG doses (11.5, 23 mg/kg) caused significant delays in incisor eruption and vaginal opening.
- Female offspring exposed to 23 mg/kg LTG exhibited hyperactivity and decreased GABA-A receptor expression.
Conclusions:
- Prenatal lamotrigine exposure can lead to significant postnatal developmental delays and behavioral alterations in rat offspring.
- The effects of LTG appear to be sex-specific, with female offspring showing notable behavioral changes.
- Further research is warranted to elucidate the mechanisms behind LTG-induced developmental and behavioral effects.
Abstract:
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.
